TECHNICAL NOTE
LCT-22018G>A single nucleotide polymorphism is a better predictor of adult-type hypolactasia/lactase persistence in Japanese-Brazilians than LCT-13910C>T
Rejane Mattar
, Maria do Socorro Monteiro, Joyce Matie Kinoshita da Silva, Flair Jose Carrilho
Corresponding author
Hospital das Clínicas da Faculdade de Medicina da USP – Gastroenterology. Av. Dr. Enéas de Carvalho Aguiar 255, 9° andar sala 9159, Cerqueira César, São Paulo, SP, Brazil, CEP 05403-000. Tel. 11-30696150, fax. 11-30697830.
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Av. Dr. Enéas de Carvalho Aguiar 255, 9° andar sala 9159, Cerqueira César, São Paulo, SP, Brazil, CEP 05403-000. Tel. 11-30696150, fax. 11-30697830." "identificador" => "aff1-cln_65p1399" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Tel.: 55 11 3069-6150" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1-" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 158 "Ancho" => 486 "Tamanyo" => 11824 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Agarose gel (2%) electrophoresis of <span class="elsevierStyleItalic">Hha</span>I-digested PCR products; M, 1kb DNA ladder (Invitrogen, USA) was used as marker of DNA fragment sizes; GA, bands of 448 bp, 264 bp, and 184 bp connote the GA genotype of three individuals; GG, two bands of 264 bp and 184bp connote the GG genotype of the other participants.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Adult type hypolactasia, the genetically programmed down-regulation of lactase enzyme activity in the intestinal wall after weaning, is a common condition worldwide, except for in northwestern Europe, where the prevalence is less than 10%. Lactose intolerant individuals complain of abdominal cramps, bloating, distention, flatulence and diarrhea after milk or lactose-containing food ingestion.<a class="elsevierStyleCrossRef" href="#bib1">1</a></p><p id="para20" class="elsevierStylePara elsevierViewall">The diagnosis of adult-type hypolactasia can be achieved by a hydrogen breath test that is cumbersome and provokes symptoms, or more recently, using a genetic approach.<a class="elsevierStyleCrossRef" href="#bib2">2</a> Lactase persistence and adult-type hypolactasia have been associated with the <span class="elsevierStyleItalic">LCT</span>-13910C>T and <span class="elsevierStyleItalic">LCT</span> -22018G>A polymorphisms in introns 13 and 9, respectively, of the minichromosome maintenance type 6 gene (<span class="elsevierStyleItalic">MCM6</span>) upstream of the <span class="elsevierStyleItalic">LCT</span> locus in several populations.<a class="elsevierStyleCrossRef" href="#bib3">3</a></p><p id="para30" class="elsevierStylePara elsevierViewall">In Brazil, the lactase persistence allele, <span class="elsevierStyleItalic">LCT</span>-13910T, was found in approximately 43% of both white (European descent) and brown (European and African descent), and 20% of black (African descent) Brazilians, but was absent in all Japanese-Brazilians studied.<a class="elsevierStyleCrossRef" href="#bib4">4</a> Recent epidemiological data regarding lactose intolerance/hypolactasia are lacking in Japan. This lack of information may be because of the relative rarity of symptoms; it has been shown that, although 92% of tested subjects were lactase deficient, only 2% were milk intolerant and 13% were lactose intolerant.<a class="elsevierStyleCrossRef" href="#bib5">5</a></p><p id="para40" class="elsevierStylePara elsevierViewall">Recent evidence in northern China suggests that <span class="elsevierStyleItalic">LCT</span>-22018G>A, rather than <span class="elsevierStyleItalic">LCT</span>-13910C>T, <span class="elsevierStyleItalic">LCT-</span>13907C>G, <span class="elsevierStyleItalic">LCT</span>-13915T>G, or <span class="elsevierStyleItalic">LCT</span>-14010G>C, matched the lactase persistence phenotype.<a class="elsevierStyleCrossRef" href="#bib6">6</a> Therefore, the purpose of this study was to ascertain whether <span class="elsevierStyleItalic">LCT</span>-22018G>A would also be a predictor of lactase persistence in Japanese-Brazilians.</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">MATERIALS AND METHODS</span><p id="para50" class="elsevierStylePara elsevierViewall">This study was approved by the local Ethics Committee. The study population consisted of 56 Japanese-Brazilians with the <span class="elsevierStyleItalic">LCT</span>-13910CC genotype according to a previously described genotyping technique,<a class="elsevierStyleCrossRef" href="#bib4">4</a> with a mean age of 47.1 ± 17.6 years. Seventeen (30.4%) men gave written informed consent to participate.</p><p id="para60" class="elsevierStylePara elsevierViewall">DNA was extracted from leukocytes. Primers 5′-AACAGGCACGTGGAGGAGTT-3′ (position 18261-18280) and 5′-CCCACCTCAGCCTCTTGAGT-3′ (position 18708-18689), Accession number <span class="elsevierStyleItalic">AY220757</span>, spanning the <span class="elsevierStyleItalic">LCT</span>-22018 region, were used in a polymerase chain reaction (PCR) with Premium <span class="elsevierStyleItalic">Taq</span> DNA polymerase (Invitrogen, São Paulo, Brazil) and 2.5 mM MgCl<span class="elsevierStyleInf">2</span>. Amplification was performed in 38 cycles at 95°C for 1 min, 67°C for 1 min, and 72°C for 1 min. The PCR product was digested with <span class="elsevierStyleItalic">Hha</span>I, resulting in one fragment of 448 bp (the AA genotype), two fragments of 264 and 184 bp (the GG genotype) and three fragments of 448, 264, and 184 bp (the GA genotype), which were visualized on a 2% agarose gel stained with ethidium bromide, as has been previously described by Büning et al.<a class="elsevierStyleCrossRef" href="#bib7">7</a></p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS AND DISCUSSION</span><p id="para70" class="elsevierStylePara elsevierViewall">Among the 56 Japanese-Brazilians who were previously genotyped as <span class="elsevierStyleItalic">LCT</span>-13910CC (hypolactasia),<a class="elsevierStyleCrossRef" href="#bib4">4</a> 3 (5.4%) had the <span class="elsevierStyleItalic">LCT</span>-22018GA genotype associated with lactase persistence (<a class="elsevierStyleCrossRef" href="#fig1">Fig. 1</a>), and 53 (94.6%) had the <span class="elsevierStyleItalic">LCT</span>-22018GG genotype associated with hypolactasia (<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>).</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><elsevierMultimedia ident="tbl1"></elsevierMultimedia><p id="para80" class="elsevierStylePara elsevierViewall">The incidence of lactase deficiency gradually increases with age from 3 years, and approximately 90% of all normal Japanese adults are lactase-deficient.<a class="elsevierStyleCrossRef" href="#bib8">8</a> Among Japanese-Brazilians, 100% had lactose malabsorption;<a class="elsevierStyleCrossRef" href="#bib9">9</a> therefore, these values are in accordance with lactose malabsorption in Japanese people who have been diagnosed by the hydrogen breath test.</p><p id="para90" class="elsevierStylePara elsevierViewall">In Brazilians, both the <span class="elsevierStyleItalic">LCT</span>-13910C>T allele<a class="elsevierStyleCrossRef" href="#bib2">2</a> and the <span class="elsevierStyleItalic">LCT</span>-22018G>A allele<a class="elsevierStyleCrossRef" href="#bib10">10</a> have been associated with lactase persistence phenotypes. As such, genetic analysis for Japanese-Brazilians should include an assessment for the <span class="elsevierStyleItalic">LCT</span>-22018G>A allele, as the <span class="elsevierStyleItalic">LCT</span>-13910C>T polymorphism is already routinely performed for hypolactasia/lactase persistence diagnosis.<a class="elsevierStyleCrossRef" href="#bib2">2</a></p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSION</span><p id="para100" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">LCT</span>-22018G>A allele is a better predictor of lactase persistence in Japanese-Brazilians than the <span class="elsevierStyleItalic">LCT</span>-13910C>T allele.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 1 => array:2 [ "identificador" => "cesec20" "titulo" => "MATERIALS AND METHODS" ] 2 => array:2 [ "identificador" => "cesec30" "titulo" => "RESULTS AND DISCUSSION" ] 3 => array:2 [ "identificador" => "cesec40" "titulo" => "CONCLUSION" ] 4 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1-" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 158 "Ancho" => 486 "Tamanyo" => 11824 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Agarose gel (2%) electrophoresis of <span class="elsevierStyleItalic">Hha</span>I-digested PCR products; M, 1kb DNA ladder (Invitrogen, USA) was used as marker of DNA fragment sizes; GA, bands of 448 bp, 264 bp, and 184 bp connote the GA genotype of three individuals; GG, two bands of 264 bp and 184bp connote the GG genotype of the other participants.</p>" ] ] 1 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Japanese-Brazilian \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="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">LCT</span>-22018GA \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="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">LCT</span>-22018GG \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="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Total \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="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">LCT</span>-13910CC \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">3 (5.4%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">53 (94.6%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">56 (100%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Genotypic distribution of lactase persistence/hypolactasia in Japanese-Brazilians.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intolerância à lactose: mudança de paradigmas com a biologia molecular" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ R Mattar \n \t\t\t\t\t\t\t\t """ 1 => """ DFC Mazo \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1590/s0104-42302010000100005" "Revista" => array:5 [ "tituloSerie" => "Rev Assoc Med Bras" "fecha" => "2010" "volumen" => "56" "paginaInicial" => "6" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20339776" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1590/s0104-42302010000100005" "WWW" => array:1 [ "link" => "https://doi.org/10.1590/S0104-42302010000200025" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Single nucleotide polymorphism C/T<span class="elsevierStyleInf">-13910</span>, located upstream of the lactase gene, associated with adult-type hypolactasia: validation for clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ R Mattar \n \t\t\t\t\t\t\t\t """ 1 => """ MS Monteiro \n \t\t\t\t\t\t\t\t """ 2 => """ CA Villares \n \t\t\t\t\t\t\t\t """ 3 => """ AF Santos \n \t\t\t\t\t\t\t\t """ 4 => """ FJ Carrilho \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1016/j.clinbiochem.2007.10.001" "Revista" => array:5 [ "tituloSerie" => "Clin Biochem" "fecha" => "2008" "volumen" => "41" "paginaInicial" => "30" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17963704" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1016/j.clinbiochem.2007.10.001" "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.clinbiochem.2008.01.006" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of a variant associated with adult-type hypolactasia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ NS Enattah \n \t\t\t\t\t\t\t\t """ 1 => """ T Sahi \n \t\t\t\t\t\t\t\t """ 2 => """ E Savilahti \n \t\t\t\t\t\t\t\t """ 3 => """ JD Terwilliger \n \t\t\t\t\t\t\t\t """ 4 => """ L Peltonen \n \t\t\t\t\t\t\t\t """ 5 => """ I Jãverlã \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Nat Genet" "fecha" => "2002" "volumen" => "30" "paginaInicial" => "7" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1038/ng826" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequency of <span class="elsevierStyleItalic">LCT-13910C</span>>T single nucleotide polymorphism associated with adult-type hypolactasia/lactase persistence among Brazilians of different ethnic groups" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ R Mattar \n \t\t\t\t\t\t\t\t """ 1 => """ MS Monteiro \n \t\t\t\t\t\t\t\t """ 2 => """ CA Villares \n \t\t\t\t\t\t\t\t """ 3 => """ AF Santos \n \t\t\t\t\t\t\t\t """ 4 => """ JMK Silva \n \t\t\t\t\t\t\t\t """ 5 => """ FJ Carrilho \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1186/1475-2891-8-46" "Revista" => array:5 [ "tituloSerie" => "Nutr J" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19799794" "web" => "Medline" ] ] ] ] 1 => array:2 [ "doi" => "10.1186/1475-2891-8-46" "WWW" => array:1 [ "link" => "https://doi.org/10.1186/1475-2891-8-46" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Milk is a useful test meal for measurement of small bowel transit time" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => """ T Kondo \n \t\t\t\t\t\t\t\t """ 1 => """ F Liu \n \t\t\t\t\t\t\t\t """ 2 => """ Y Toda \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Gastroenterol" "fecha" => "1994" "volumen" => "29" "paginaInicial" => "20" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1007/BF02349276" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The -22018A allele matches the lactase persistence phenotype in northern Chinese populations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ L Xu \n \t\t\t\t\t\t\t\t """ 1 => """ H Sun \n \t\t\t\t\t\t\t\t """ 2 => """ X Zhang \n \t\t\t\t\t\t\t\t """ 3 => """ J Wang \n \t\t\t\t\t\t\t\t """ 4 => """ D Sun \n \t\t\t\t\t\t\t\t """ 5 => """ F Chen \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Scand J Gastroenterol" "fecha" => "2010" "volumen" => "45" "paginaInicial" => "174" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.3109/00365520903414176" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The C/C-13910 and G/G-22018 genotypes for adult-type hypolactasia are not associated with inflammatory bowel disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => """ C Büning \n \t\t\t\t\t\t\t\t """ 1 => """ J Ockenga \n \t\t\t\t\t\t\t\t """ 2 => """ S Krüger \n \t\t\t\t\t\t\t\t """ 3 => """ J Jurga \n \t\t\t\t\t\t\t\t """ 4 => """ P Baier \n \t\t\t\t\t\t\t\t """ 5 => """ A Dignass \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Scand J Gastroenterol" "fecha" => "2003" "volumen" => "38" "paginaInicial" => "42" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breath hydrogen test for detecting lactose malabsorption in infants and children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => """ O Nose \n \t\t\t\t\t\t\t\t """ 1 => """ Y Iida \n \t\t\t\t\t\t\t\t """ 2 => """ H Kai \n \t\t\t\t\t\t\t\t """ 3 => """ T Harada \n \t\t\t\t\t\t\t\t """ 4 => """ M Ogawa \n \t\t\t\t\t\t\t\t """ 5 => """ H Yabuuchi \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Arch Dis Child" "fecha" => "1979" "volumen" => "54" "paginaInicial" => "40" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1136/adc.54.6.436" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Primary lactose malabsorption in healthy Brazilian adult caucasoid, negroid and mongoloid subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => """ A Sevá-Pereira \n \t\t\t\t\t\t\t\t """ 1 => """ B Beiguelman \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Arq Gastroenterol" "fecha" => "1982" "volumen" => "19" "paginaInicial" => "8" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lactase persistence/non-persistence variants, C/T_13910 and G/A_22018, as a diagnostic tool for lactose intolerance in IBS patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => """ CF Bernardes-Silva \n \t\t\t\t\t\t\t\t """ 1 => """ AC Pereira \n \t\t\t\t\t\t\t\t """ 2 => """ GFA da Mota \n \t\t\t\t\t\t\t\t """ 3 => """ JE Krieger \n \t\t\t\t\t\t\t\t """ 4 => """ AA Laudanna \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2007" "volumen" => "386" "paginaInicial" => "11" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://doi.org/10.1016/j.cca.2007.07.012" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/0000006500000012/v1_202212011539/S1807593222016167/v1_202212011539/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/0000006500000012/v1_202212011539/S1807593222016167/v1_202212011539/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222016167?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 0 | 9 |
| 2024 October | 21 | 19 | 40 |
| 2024 September | 31 | 16 | 47 |
| 2024 August | 37 | 27 | 64 |
| 2024 July | 35 | 25 | 60 |
| 2024 June | 36 | 10 | 46 |
| 2024 May | 48 | 11 | 59 |
| 2024 April | 25 | 10 | 35 |
| 2024 March | 37 | 15 | 52 |
| 2024 February | 32 | 10 | 42 |
| 2024 January | 39 | 18 | 57 |
| 2023 December | 25 | 16 | 41 |
| 2023 November | 16 | 26 | 42 |
| 2023 October | 39 | 29 | 68 |
| 2023 September | 36 | 15 | 51 |
| 2023 August | 23 | 9 | 32 |
| 2023 July | 30 | 17 | 47 |
| 2023 June | 37 | 17 | 54 |
| 2023 May | 70 | 2 | 72 |
| 2023 April | 53 | 1 | 54 |
| 2023 March | 46 | 4 | 50 |
| 2023 February | 42 | 0 | 42 |
| 2023 January | 18 | 3 | 21 |
| 2022 December | 14 | 3 | 17 |
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