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CLINICAL SCIENCE
The ADA∗2 allele of the adenosine deaminase gene (20q13.11) and recurrent spontaneous abortions: an age-dependent association
Daniela Prudente Teixeira NunesI, Lígia Cosentino Junqueira Franco SpegiorinII,III, Cinara Cássia Brandão de MattosI, Antonio Helio OlianiII,III, Denise Cristina Mós Vaz-OlianiII,III, Luiz Carlos de MattosI,
Corresponding author
I Faculdade de Medicina de São José do Rio Preto (FAMERP), Immunogenetics Laboratory, Molecular Biology Department - São José do Rio Preto, SP, Brazil.
II Faculdade de Medicina de São José do Rio Preto (FAMERP), Gynecology and Obstetrics Department, São José do Rio Preto, SP, Brazil.
III Hospital de Base - Fundação Faculdade Regional de Medicina de São José do Rio Preto (HB-FUNFARME), Gynecology and Obstetrics Outpatient Clinic, São José do Rio Preto, SP, Brazil.
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">The electrophoretic profile of the fragment of 397 base pairs &#40;bp&#41; of exon 1 of the <span class="elsevierStyleItalic">ADA</span> gene after digestion with the Taq I enzyme showing the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> &#40;1&#41;&#44; <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> &#40;2&#41; and <span class="elsevierStyleItalic">ADA&#8727;2&#47;&#8727;2</span> &#40;3&#41; genotypes and the marker &#40;L&#41; of 100 base pairs&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Recurrent spontaneous abortion &#40;RSA&#41; is defined by two or more consecutive miscarriages before 20 weeks of gestation&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;2</a> The etiology of RSA is varied&#44; but immunological&#44; anatomical&#44; endocrine&#44; and genetic aspects are considered the most important factors&#46; These factors may act on fetus selection in such a way as to impede the implantation of the zygote or to prevent fertilization&#46;<a class="elsevierStyleCrossRef" href="#bib3">3</a></p><p id="para20" class="elsevierStylePara elsevierViewall">The enzyme adenosine deaminase &#40;ADA&#59; EC 3&#46;5&#46;4&#46;4&#41; catalyzes the deamination of adenosine and deoxyadenosine&#44; thereby affecting the methylation process&#44; cell growth and differentiation&#44; apoptosis&#44; DNA replication and immune functions&#46;<a class="elsevierStyleCrossRefs" href="#bib4">4&#44;5</a> The genetic deficiency of ADA in humans results in severe combined immunodeficiency syndrome &#40;SCID&#41; of both the humoral and cellular immune responses&#46;<a class="elsevierStyleCrossRef" href="#bib6">6</a> The polymorphism of the <span class="elsevierStyleItalic">ADA</span> gene &#40;20q13&#46;11&#41; resulting from the substitution of G by A at nucleotide 22 of exon 1 replaces the Asp amino acid &#40;<span class="elsevierStyleItalic">ADA&#8727;1</span> allele&#41; with Asn &#40;<span class="elsevierStyleItalic">ADA&#8727;2</span> allele&#41; amino acid in position 8 of the enzyme&#46; Consequently&#44; individuals with the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele express low levels of ADA compared to homozygous <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> individuals&#46;<a class="elsevierStyleCrossRef" href="#bib7">7</a></p><p id="para30" class="elsevierStylePara elsevierViewall">ADA activity is critical in maintaining a normal pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib8">8&#44;9</a> In a previous report&#44; Nicotra et al&#46;<a class="elsevierStyleCrossRef" href="#bib10">10</a> observed that the frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele is lower in European women who suffer RSA than those who do not&#44; suggesting a protective effect of this allele against RSA and higher fertility rates among women with <span class="elsevierStyleItalic">ADA&#8727;2</span> allele&#46; Recently&#44; these same authors observed a synergic effect of <span class="elsevierStyleItalic">ACP1</span> &#40;low molecular weight protein tyrosine phosphatase&#41; and <span class="elsevierStyleItalic">ADA</span> polymorphisms with respect to RSA&#46;<a class="elsevierStyleCrossRef" href="#bib11">11</a> These authors concluded that women with high ADA activity and low ACP1 activity have a higher susceptibility to RSA&#46; A European ethnic background is present in the Brazilian population&#44;<a class="elsevierStyleCrossRef" href="#bib12">12</a> but data are scarce on the importance of the <span class="elsevierStyleItalic">ADA G22A</span> genetic polymorphism in RSA in Brazilian women&#46; The aim of this study was to investigate whether the <span class="elsevierStyleItalic">ADA G22A</span> polymorphism is associated with RSA in Brazilian women&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">PATIENTS AND METHODS</span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Ethical considerations</span><p id="para40" class="elsevierStylePara elsevierViewall">This study was approved by the Research Ethics Committee of the Medical School in S&#227;o Jos&#233; do Rio Preto - FAMERP &#40;&#35; 308&#47;2008&#41;&#46; The objectives of the investigation and all procedures performed in the study were explained to selected patients&#44; and those who agreed to participate in the study gave their written consent&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Patient selection</span><p id="para50" class="elsevierStylePara elsevierViewall">Two groups of pregnant women were selected from the Gynecology and Obstetrics Clinic&#44; Hospital de Base from the Regional Medical School Foundation in S&#227;o Jos&#233; do Rio Preto&#44; S&#227;o Paulo State&#44; Brazil&#46; The first group &#40;G1&#44; N &#61; 129&#41; included only women who had suffered at least two consecutive spontaneous abortions with the same partner according to their medical records and to reports from the patients themselves&#46; The second group &#40;G2&#44; N &#61; 182&#41; included only women with at least two successive spontaneously conceived pregnancies and no history of spontaneous abortion&#46; Patients who were younger than 18 years old were excluded from the study&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Data collection</span><p id="para60" class="elsevierStylePara elsevierViewall">An epidemiological questionnaire was completed by all participating patients&#44; and these data were later confirmed with their medical records&#46; Comorbidities such as a history of diabetes&#44; hypertension&#44; polycystic ovarian syndrome&#44; uterine malformation&#44; antiphospholipid antibodies&#44; and endometriosis were also collected from the medical records&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Collection of blood samples and genomic DNA extraction</span><p id="para70" class="elsevierStylePara elsevierViewall">Five milliliters of peripheral blood was collected from each participant in tubes containing EDTA anticoagulant&#46; Genomic DNA was extracted from 200 &#956;L of whole blood using a commercial kit &#40;PureLink&#8482; Genomic DNA Mini Kit&#44; Invitrogen&#41;&#46; The manufacturer&#39;s instructions were strictly followed&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Identification of the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles</span><p id="para80" class="elsevierStylePara elsevierViewall">The identification of the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles was achieved using PCR-RFLP analysis following the protocol of Safranow et al&#46;<a class="elsevierStyleCrossRef" href="#bib13">13</a> A gene amplification reaction &#40;25 &#956;L final volume&#41; was performed for each sample of genomic DNA under the following conditions&#58; 7&#46;2 &#956;L of MilliQ water&#44; 5&#46;0 &#956;L of PCR Buffer Green &#40;5x&#44; Promega&#41;&#44; 1&#46;5 &#956;L MgCl<span class="elsevierStyleInf">2</span> &#40;25 mM&#44; Promega&#41;&#44; 2&#46;1 &#956;L of DMSO &#40;Nuclear&#41;&#44; 1&#46;0 &#956;L of 2-mercapto-ethanol &#40;200 mM&#44; Vetec&#41;&#44; 1&#46;0 &#956;L of sense primer &#40;5 pM&#44; IDT&#59; 5&#8242;-GCCCGGCCCGTTAAGAAGAGC-3&#8242;&#41;&#44; 1&#46;0 &#956;L of antisense primer &#40;5 pM&#44; IDT&#59; 5&#8242;- GGTCAAGTCAGGGGCAGAAGCAGA-3&#8242;&#41;&#44; 4&#46;0 &#956;L of dNTPs &#40;1&#46;25 mM&#44; Invitrogen&#41;&#44; 0&#46;2 &#956;L of GoTaq Hot Start DNA polymerase &#40;5 U&#44; Promega&#41;&#44; and 2&#46;0 &#956;L of genomic DNA&#46; As an internal contamination control&#44; a tube was prepared under identical conditions but without the genomic DNA &#40;blank&#41;&#46; The amplification conditions were as follows&#58; 94&#176;C for 15 minutes&#44; 36 cycles of 94&#176;C for 40 seconds&#44; 66&#176;C for 80 seconds&#44; 72&#176;C for 80 seconds&#44; and 1 cycle of 72&#176;C for 8 min&#44; with the product remaining at 4&#176;C ad infinitum&#46; The amplified 397 bp fragment was analyzed by 2&#37; agarose gel electrophoresis &#40;Invitrogen&#41; and ethidium bromide staining &#40;Invitrogen&#41;&#46; The PCR product &#40;7&#46;0 &#956;L&#41; was incubated at 65&#176;C with 0&#46;7 &#956;L of <span class="elsevierStyleItalic">Taq I</span> Fast Digest &#40;1 U&#44; Fermentas&#41; and 1&#46;34 &#956;L of enzyme buffer &#40;10x&#44; Fermentas&#41; for 20 minutes&#46; After an electrophoresis run of 30 minutes at 100 volts in 2&#37; agarose gel &#40;Invitrogen&#41;&#44; the fragments were viewed using ethidium bromide staining&#46; The PCR product corresponding to the <span class="elsevierStyleItalic">ADA&#8727;1</span> allele &#40;G22&#41; was then cleaved into two fragments&#58; a 245 bp fragment and a 152 bp fragment&#46; The <span class="elsevierStyleItalic">ADA&#8727;2</span> allele &#40;22A&#41; was identified by the absence of the <span class="elsevierStyleItalic">Taq</span> I restriction site&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Statistical analysis</span><p id="para90" class="elsevierStylePara elsevierViewall">The GraphPad Instat computer program version 3&#46;06 was used for all statistical calculations&#46; Fisher&#39;s exact test was used to detect differences in the distribution of <span class="elsevierStyleItalic">ADA</span> genotypes and alleles with respect to RSA&#59; a 5&#37; alpha error was considered acceptable&#46; The differences between mean values for categorical data were calculated by the unpaired t test&#46; Odds ratios and 95&#37; confidence intervals were also calculated&#46; The chi-square test was applied to compare the overall frequencies of <span class="elsevierStyleItalic">ADA</span> genotypes and verify whether the distribution of the <span class="elsevierStyleItalic">ADA</span> genotypes was in Hardy-Weinberg equilibrium using the Online Encyclopedia for Genetic Epidemiology studies &#40;OEGE&#41; &#40;<a href="http://www.oege.org/software/hwe-mr-calc.shtml">http&#58;&#47;&#47;www&#46;oege&#46;org&#47;software&#47;hwe-mr-calc&#46;shtml</a>&#41;&#46;</p></span></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">RESULTS</span><p id="para100" class="elsevierStylePara elsevierViewall">This study evaluated women with &#40;G1&#41; and without &#40;G2&#41; a history of RSA&#46; There were statistically significant differences with respect to the mean age &#40;G1&#58; 31&#46;9&#177;5&#46;7 vs&#46; G2&#58; 29&#46;2&#177;5&#46;8&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41; and average number of pregnancies &#40;G1&#58; 4&#46;6&#177;1&#46;5 vs&#46; G2&#58; 3&#46;5&#177;0&#46;9&#59; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#46; The mean number of spontaneous abortions in G1 was 2&#46;7 &#40;&#177;0&#46;8&#41;&#44; ranging from 2 to 6&#44; and the average numbers of live births in G1 and G2 were 0&#46;5 &#40;&#177;0&#46;3&#41; and 2&#46;6 &#40;&#177;1&#46;0&#41;&#44; respectively &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;0001&#41;&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">The identification of <span class="elsevierStyleItalic">ADA</span> genotypes was accomplished based on the electrophoretic profile of the 397 bp fragment of exon 1 of the <span class="elsevierStyleItalic">ADA</span> gene after digestion with the <span class="elsevierStyleItalic">Taq</span> I enzyme &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>&#41;&#46; The <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> genotypes were found in G1 and G2&#44; but just one patient with the <span class="elsevierStyleItalic">ADA&#8727;2&#47;&#8727;2</span> genotype was observed in G2 &#40;<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#41;&#46; The distributions of the <span class="elsevierStyleItalic">ADA</span> genotypes were found to be in Hardy-Weinberg equilibrium in G1 &#40;&#967;2 &#61; 0&#46;26&#44; DF 1&#41; and G2 &#40;&#967;2 &#61; 0&#46;57&#44; DF 1&#41;&#46; The frequencies of the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span>&#44; <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> and <span class="elsevierStyleItalic">ADA&#8727;2&#47;&#8727;2</span> genotypes were similar and showed no statistically significant differences &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;6771&#44; &#967;2 &#61; 0&#46;78&#59; DF 2&#41;&#46; The differences remained insignificant even when the comparison between G1 and G2 was restricted to the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> and <span class="elsevierStyleItalic">ADA&#8727;2&#47;&#8727;2</span> genotypes &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;8342&#44; OR &#61; 1&#46;177&#44; 95&#37; CI &#61; 0&#46;536-2&#46;586&#41;&#46; Although the frequencies of the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles were different in G1 and G2&#44; the difference was not statistically significant &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;7050&#44; OR&#58; 1&#46;237&#44; 95&#37; CI&#58; 0&#46;578-2&#46;646&#41;&#46;</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para120" class="elsevierStylePara elsevierViewall">A comparative analysis of the frequencies of the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles when controlling for age revealed statistically significant differences between the G1 and G2 groups &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl2"></elsevierMultimedia><p id="para130" class="elsevierStylePara elsevierViewall">The data for G1&#44; grouped according to the <span class="elsevierStyleItalic">ADA</span> genotypes &#40;<span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span>&#41;&#44; are shown in <a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>&#46; There were no statistically significant differences in the mean age&#44; average number of pregnancies&#44; number of live births or comorbidities between women with the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> genotype and those with the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> genotype&#46; Controlling for comorbidities&#44; these analyses were not statistically significant &#40;diabetes&#58; OR&#58; 0&#46;385&#44; CI 95&#37;&#58; 0&#46;045-3&#46;297&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;3601&#59; hypertension&#58; OR&#58; 1&#46;817&#44; CI 95&#37;&#58; 0&#46;235-14&#46;017&#44; <span class="elsevierStyleItalic">p</span> &#61; 1&#46;000&#59; polycystic ovarian syndrome&#58; OR&#58; 4&#46;120&#44; CI 95&#37;&#58; 0&#46;243-69&#46;710&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;3984&#59; uterine malformation&#58; OR&#58; 1&#46;411&#44; CI 95&#37;&#58; 0&#46;080-24&#46;737&#44; <span class="elsevierStyleItalic">p</span> &#61; 1&#46;000&#59; antiphospholipid antibodies&#58; OR&#58; 1&#46;046&#44; CI 95&#37;&#58; 0&#46;132-8&#46;241&#44; <span class="elsevierStyleItalic">p</span> &#61; 1&#46;000&#59; endometriosis&#58; OR&#58; 0&#46;569&#44; CI 95&#37;&#58; 0&#46;159-2&#46;031&#44; <span class="elsevierStyleItalic">p</span> &#61; 0&#46;4198&#41;&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">DISCUSSION</span><p id="para140" class="elsevierStylePara elsevierViewall">The aim of this study was to investigate the association between the <span class="elsevierStyleItalic">G22A</span> polymorphism of the <span class="elsevierStyleItalic">ADA</span> gene in Brazilian women with a history of RSA&#46; Because much of the Brazilian population has a clear European ancestry&#44;<a class="elsevierStyleCrossRef" href="#bib12">12</a> we postulated that the <span class="elsevierStyleItalic">ADA G22A</span> genetic polymorphism might be associated with RSA in Brazilian women&#46; The series of this study is representative of the population of the northwestern region of S&#227;o Paulo State&#44; which is chiefly composed of Italian&#44; Spanish&#44; Portuguese&#44; and African descendants&#46;<a class="elsevierStyleCrossRef" href="#bib14">14</a> To avoid possible bias&#44; a control group was formed of women who had at least two successful pregnancies and no history of miscarriages&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">The women who had experienced RSA who were enrolled in this study &#40;G1&#41; had a higher mean age compared to those who had not &#40;G2&#41;&#46; This difference may result from the fact that women without risk factors for spontaneous abortions achieve reproductive success and their desired number of children at an earlier age&#44; whereas women with reproductive problems are encouraged to persist longer in their attempts to conceive and reproduce&#46;<a class="elsevierStyleCrossRef" href="#bib15">15</a> Moreover&#44; older age is a risk factor for RSA&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;3</a> This observation is supported by data from a recent demographic survey carried out in Brazil&#44; which showed that maternal age of higher than 35 years contributes to an increased prevalence of RSA&#46;<a class="elsevierStyleCrossRef" href="#bib16">16</a></p><p id="para160" class="elsevierStylePara elsevierViewall">In the present study&#44; women who had experienced RSA became pregnant a significantly higher number of times than those who had not&#46; Spontaneous abortions were confirmed based on clinically recognized pregnancy losses before 20 weeks of gestation&#59; this condition has great predictive value for establishing the occurrence of unsuccessful pregnancies&#46;<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;3</a> Women who experience RSA persist in attempts to become pregnant even if the pregnancy does not often reach full term&#46; Moreover&#44; there is evidence that some early fetal losses are not clinically recognized in women with a predisposition to RSA because these pregnancies do not last long enough to be characterized as such&#46; These fetal losses are not included in the statistics&#44; and the rate of spontaneous abortions is therefore underestimated&#46;<a class="elsevierStyleCrossRef" href="#bib17">17</a></p><p id="para170" class="elsevierStylePara elsevierViewall">Several women in G1 gave birth to live babies&#44; but the average number of births was lower than those in G2&#46; This finding is consistent with the finding that women at low risk for RSA are more likely to produce children&#46; Moreover&#44; in women at risk for RSA&#44; the chance of spontaneous abortions increases with each fetal loss&#46;<a class="elsevierStyleCrossRefs" href="#bib18">18&#44;19</a> It seems that reproductive success is achieved at a younger age&#44; especially when mothers have no risk factors for RSA&#44; contributing to a greater number of live births in this group&#46;<a class="elsevierStyleCrossRefs" href="#bib16">16&#44;19</a></p><p id="para180" class="elsevierStylePara elsevierViewall">The frequencies of <span class="elsevierStyleItalic">ADA</span> genotypes and the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles were similar between G1 and G2 and were not associated with the occurrence of RSA&#46; Hence&#44; from a preliminary overview&#44; the results presented in this study are different from those observed for Italian women in whom the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele was associated with a lower risk of RSA&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;11</a></p><p id="para190" class="elsevierStylePara elsevierViewall">Different factors may contribute to the differences observed&#46; It is possible that the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele has a low frequency in the Brazilian female population as a result of ethnic mixing and that its protective effect is overshadowed by other determinants of RSA&#46; In fact&#44; population analysis revealed that the frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele is 0&#46;12 in Caucasians and varies between 0&#46;03 and 0&#46;04 in African descendants&#46;<a class="elsevierStyleCrossRefs" href="#bib7">7&#44;20</a> The frequencies of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele found in both groups of this study were lower than those reported for Caucasians but very close to those observed in African descendants&#46; Because much of the population of the northwestern region of S&#227;o Paulo State has African ancestry&#44;<a class="elsevierStyleCrossRef" href="#bib14">14</a> this characteristic could contribute to the reduced frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele in the casuistic analyzed in this study&#46;</p><p id="para200" class="elsevierStylePara elsevierViewall">The frequency of the <span class="elsevierStyleItalic">ADA G22A</span> genetic polymorphism in different Brazilian regions has been little explored&#46; A recent study found that the frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele in healthy men and women in the State of Rio Grande do Sul is 11&#46;7&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib21">21</a> This percentage is approximately twice that found in the present study&#44; but the ethnic background of the population of southern Brazil is different from that of the northwestern region of S&#227;o Paulo State&#46;<a class="elsevierStyleCrossRefs" href="#bib14">14&#44;22&#44;23</a> It is possible that the frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele among Brazilians is influenced by ethnic and racial admixture&#46; Investigations focusing the <span class="elsevierStyleItalic">ADA G22A</span> polymorphism in other regions of Brazil could confirm this proposition&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">ADA</span> genotypes and alleles were compared between the G1 and G2 groups when controlling for maternal age because this variable was found to be associated with the risk for RSA&#46; The results did not reveal statistically significant differences in the frequency of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele among those aged 35 years or younger&#44; whereas an association between this allele and low risk for RSA was observed for women older than 35 years of age&#46;</p><p id="para220" class="elsevierStylePara elsevierViewall">The role of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele in reducing the risk of RSA is not completely understood&#46; The presence of an <span class="elsevierStyleItalic">ADA&#8727;2</span> allele reduces ADA enzyme expression to between 15 and 20&#37; of that found in the homozygous <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> genotype&#44; which enables an increase in adenosine levels&#46;<a class="elsevierStyleCrossRef" href="#bib7">7</a> Consequently&#44; carriers of at least one <span class="elsevierStyleItalic">ADA&#8727;2</span> allele have higher levels of circulating and intracellular adenosine&#46;<a class="elsevierStyleCrossRef" href="#bib24">24</a></p><p id="para230" class="elsevierStylePara elsevierViewall">Because adenosine acts as a hormone that regulates blood flow&#44; neurotransmission and platelet aggregation and is a potent vasodilator&#44;<a class="elsevierStyleCrossRefs" href="#bib25">25&#44;26</a> its presence in the uterus and the placenta could contribute to a reduced rate of early loss of zygotes or fetuses&#44; thus protecting <span class="elsevierStyleItalic">ADA&#8727;2</span>-carrying women against RSA&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;11</a> This protection may be especially relevant for women older than 35 years of age&#46; Additionally&#44; the increased adenosine resulting from the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele could contribute to vascular integrity&#44; thus increasing uterine and placental blood flow&#46;<a class="elsevierStyleCrossRef" href="#bib9">9</a> Therefore&#44; evaluations of ADA levels at different times during the gestational period among women carrying distinct <span class="elsevierStyleItalic">ADA</span> genotypes could help to clarify the potential effects of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele during successful pregnancies and shed additional light on the biological and clinical impact of this enzyme on RSA and in assisted reproduction&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">Different studies have observed low frequencies of the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele in couples with sterility problems&#44; women suffering from RSA&#44; those with great variability in gestation time and those who have low birth weight newborns&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;11</a> Because this enzyme has an important role in modulating the immune response&#44; a reduction in its expression seems to affect the fertility rate of women older than 35 years of age&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">To assess the differential effects of the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles on miscarriages&#44; the comorbidities of pregnant women in G1 with the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> genotypes were compared&#46; There were no statistically significant differences in mean age&#44; the average numbers of pregnancies and spontaneous abortions&#44; the average number of live births&#44; diabetes &#40;including pregnancy-related and type II diabetes&#41;&#44; hypertension&#44; polycystic ovarian syndrome&#44; uterine malformations&#44; antiphospholipid antibodies or endometriosis&#46; Therefore&#44; the <span class="elsevierStyleItalic">ADA&#8727;1</span> and <span class="elsevierStyleItalic">ADA&#8727;2</span> alleles&#44; when controlled for comorbidities&#44; are not associated with the presence or absence of RSA&#46; These comorbidities are associated with miscarriages&#44; but their influence may be independent of the <span class="elsevierStyleItalic">ADA</span> alleles and genotypes&#46;</p><p id="para260" class="elsevierStylePara elsevierViewall">The small number of <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> women in G1&#44; which reduces the power of the test<span class="elsevierStyleUnderline">&#44;</span> does not allow an analysis of whether either allele provides a biological advantage with respect to early fetal loss as established by other determinants of RSA&#46;</p><p id="para270" class="elsevierStylePara elsevierViewall">In summary&#44; the data of this study show that the risk for RSA increases with maternal age and that the <span class="elsevierStyleItalic">ADA&#8727;2</span> allele of the <span class="elsevierStyleItalic">ADA</span> gene is associated with low risk of RSA among older women&#46;</p></span></span>"
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        1 => array:2 [
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          "titulo" => "INTRODUCTION"
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          "titulo" => "PATIENTS AND METHODS"
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              "titulo" => "Ethical considerations"
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              "titulo" => "Patient selection"
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              "titulo" => "Data collection"
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              "identificador" => "cesec60"
              "titulo" => "Collection of blood samples and genomic DNA extraction"
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            4 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Identification of the ADA&#8727;1 and ADA&#8727;2 alleles"
            ]
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              "identificador" => "cesec80"
              "titulo" => "Statistical analysis"
            ]
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          "titulo" => "RESULTS"
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        4 => array:2 [
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          "titulo" => "DISCUSSION"
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        5 => array:2 [
          "identificador" => "xack639343"
          "titulo" => "ACKNOWLEDGEMENTS AND FUNDING"
        ]
        6 => array:1 [
          "titulo" => "REFERENCES"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2011-07-15"
    "fechaAceptado" => "2011-07-22"
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          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1582453"
          "palabras" => array:3 [
            0 => "Adenosine deaminase"
            1 => "Recurrent spontaneous abortions"
            2 => "<span class="elsevierStyleItalic">ADA</span> gene"
          ]
        ]
      ]
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE&#58;</span><p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response&#46; The adenosine deaminase <span class="elsevierStyleItalic">G22A</span> polymorphism &#40;20q&#46;11&#46;33&#41; influences the level of adenosine deaminase enzyme expression&#44; which seems to play a key role in maintaining pregnancy&#46; The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women&#46; The aim of this study was to investigate whether the <span class="elsevierStyleItalic">G22A</span> polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara60" class="elsevierStyleSimplePara elsevierViewall">A total of 311 women were recruited to form two groups&#58; G1&#44; with a history of recurrent spontaneous abortions &#40;N &#61; 129&#41;&#44; and G2&#44; without a history of abortions &#40;N &#61; 182&#41;&#46; Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the <span class="elsevierStyleItalic">G22A</span> genetic polymorphism&#46; Fisher&#39;s exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion &#40;<span class="elsevierStyleItalic">p</span>&#60;0&#46;05&#41;&#46; The differences between mean values for categorical data were calculated using unpaired t tests&#46; The Hardy-Weinberg equilibrium was assessed with a chi-square test&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS&#58;</span><p id="spara80" class="elsevierStyleSimplePara elsevierViewall">The results suggest that the adenosine deaminase <span class="elsevierStyleItalic">&#8727;2</span> allele is associated with a low risk for recurrent spontaneous abortions&#44; but this association is dependent on older age&#46;</p></span>"
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            "titulo" => "RESULTS&#58;"
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        "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported&#46;</p> <p class="elsevierStyleNotepara" id="cenpara20">Nunes DPT and Spegiorin LCJF contribute equally like first author&#46; Nunes DPT and Brand&#227;o de Mattos CC performed the genomic analysis&#46; Spegiorin LCJF&#44; Oliani AH and Vaz-Oliani DCM are MD and selected the casuistic and provided samples&#46; de Mattos LC conceived the study and prepared the manuscript&#46;</p>"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">The electrophoretic profile of the fragment of 397 base pairs &#40;bp&#41; of exon 1 of the <span class="elsevierStyleItalic">ADA</span> gene after digestion with the Taq I enzyme showing the <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;1</span> &#40;1&#41;&#44; <span class="elsevierStyleItalic">ADA&#8727;1&#47;&#8727;2</span> &#40;2&#41; and <span class="elsevierStyleItalic">ADA&#8727;2&#47;&#8727;2</span> &#40;3&#41; genotypes and the marker &#40;L&#41; of 100 base pairs&#46;</p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G1 &#40;N &#61; 129&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G2 &#40;N &#61; 182&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">OR<a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">CI 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tfn2">&#8727;&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">ADA genotypes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">91&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">164&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">90&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;177&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;536 &#8211; 2&#46;586&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;8435&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;904&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;408 &#8211; 2&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;8436&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">2&#47;</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;426&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;017 &#8211; 10&#46;552&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;0000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleBold">Alleles</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">247&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">95&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">345&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">94&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;237&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;578 &#8211; 2&#46;646&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;7050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn1">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">5&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  """
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotypes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G1 &#40;N &#61; 129&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">G2 &#40;N &#61; 182&#41;</th><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">35 or younger&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">N &#61; 85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">N &#61; 155&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">OR<a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">CI 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tfn4">&#8727;&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">89&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">146&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">94&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;5205&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;198 &#8211; 1&#46;366&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;2042&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Alleles&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">94&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">97&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;5349&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;208 &#8211; 1&#46;374&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;2126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">5&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
            1 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t  " align="left" valign="top" scope="col">Older than 35&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#40;N &#61; 44&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col">&#40;N &#61; 27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="top">42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">95&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">66&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">10&#46;500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;059 &#8211; 53&#46;539&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">29&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;1131&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;021 &#8211; 0&#46;584&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2&#47;</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;1985&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;007 &#8211; 5&#46;055&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;3803&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">Alleles</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">97&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">81&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;773&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;051 &#8211; 46&#46;573&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn3">&#8727;</a><span class="elsevierStyleItalic">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">18&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tfn3"
              "etiqueta" => "&#8727;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara50">Adjusted odds ratio&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tfn4"
              "etiqueta" => "&#8727;&#8727;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara60">Calculated by Fisher&#39;s exact test&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">A comparison of the frequencies of <span class="elsevierStyleItalic">ADA</span> alleles and genotypes in women with &#40;G1&#41; and without &#40;G2&#41; RSA aged 35 years or younger and those older than 35 years of age&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl3"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="top" scope="col">Characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1</span> &#40;N &#61; 118&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="top" scope="col"><span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">2</span> &#40;N &#61; 11&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-value<a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Mean age &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">32&#46;1 &#40;&#177;5&#46;7&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">30&#46;0 &#40;&#177;5&#46;1&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;2301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Pregnancies &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">4&#46;7 &#40;&#177;1&#46;5&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">3&#46;6 &#40;&#177;1&#46;1&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;2417&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Live births &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">0&#46;7 &#40;&#177;0&#46;5&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">0&#46;5 &#40;&#177;0&#46;3&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;1953&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Miscarriages &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">2&#46;7 &#40;&#177;0&#46;8&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="center" valign="top">2&#46;5 &#40;&#177;0&#46;6&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;6765&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top"><span class="elsevierStyleItalic">p</span>-value <a class="elsevierStyleCrossRef" href="#tfn6">&#8727;&#8727;</a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;3030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">13&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;0000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Polycystic ovarian syndrome&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">15&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;3607&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Uterine malformation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;0000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top">Antiphospholipid antibodies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">9&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top">1&#46;0000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="top" style="border-bottom: 2px solid black">Endometriosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">9&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">27&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="top" style="border-bottom: 2px solid black">0&#46;1602&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tfn5"
              "etiqueta" => "&#8727;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara70">Calculated by an unpaired t test&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tfn6"
              "etiqueta" => "&#8727;&#8727;"
              "nota" => "<p class="elsevierStyleNotepara" id="cenpara80">Calculated by Fisher&#39;s exact test&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">The demographic characteristics&#44; reproductive histories and comorbidities of women who had suffered two or more recurrent spontaneous abortions according to the <span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1</span> and <span class="elsevierStyleItalic">ADA</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">1&#47;</span><a class="elsevierStyleCrossRef" href="#tfn5">&#8727;</a><span class="elsevierStyleItalic">2</span> genotypes &#40;N &#61; 129&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recurrent Miscarriage"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              R Rai \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              L Regan \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2006"
                        "volumen" => "9535"
                        "paginaInicial" => "601"
                        "paginaFinal" => "611"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "10&#46;1016&#47;S0140-6736&#40;06&#41;69204-0"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib2"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "International Committee for Monitoring Assisted Reproductive Technology &#40;ICMART&#41; and the World Health Organization &#40;WHO&#41; revised glossary of ART terminology&#44; 2009"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => """
                              F Zegers-Hochschild \n
                              \t\t\t\t\t\t\t\t
                              """
                            1 => """
                              GD Adamson \n
                              \t\t\t\t\t\t\t\t
                              """
                            2 => """
                              J de Mouzon \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              O Ishihara \n
                              \t\t\t\t\t\t\t\t
                              """
                            4 => """
                              R Mansour \n
                              \t\t\t\t\t\t\t\t
                              """
                            5 => """
                              K Nygren \n
                              \t\t\t\t\t\t\t\t
                              """
                          ]
                        ]
                      ]
                    ]
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        "texto" => "<p id="para280" class="elsevierStylePara elsevierViewall">This work was supported by the Higher Education Professional Training Board &#40;CAPES&#41; &#8211; Ministry of Education&#44; Brazilian Government &#40;to CCBM and DPTN&#41;&#44; and by a research grant from the Medical School in S&#227;o Jos&#233; do Rio Preto - BAP-FAMERP &#40;to AHO and LCM&#41;&#46;</p>"
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ISSN: 18075932
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

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