Special article
Human genetics ability to predict the risk of suffering an infectious disease
Capacidad de la genética humana de predecir el riesgo de presentar una enfermedad infecciosa
Raquel Moreno Mayordomoa,
, Irene López Ramosb, Raúl Ortiz de Lejarazu Leonardoc
Corresponding author
a Servicio de Análisis Clínicos, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
b Servicio de Microbiología e Inmunología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
c Servicio de Microbiología e Inmunología, Hospital Clínico Universitario de Valladolid, Centro Nacional de Gripe, Valladolid, Spain
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[ 0 => "morenomayordomo@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Irene" "apellidos" => "López Ramos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Raúl" "apellidos" => "Ortiz de Lejarazu Leonardo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Análisis Clínicos, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Microbiología e Inmunología, Hospital Clínico Universitario de Valladolid, Valladolid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Microbiología e Inmunología, Hospital Clínico Universitario de Valladolid, Centro Nacional de Gripe, Valladolid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Capacidad de la genética humana de predecir el riesgo de presentar una enfermedad infecciosa" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The discovery of the genetic code and the subsequent development of molecular biology have led to a paradigm shift to understand biology, and thus, the concepts of health and disease have evolved. The revolution caused by the development of the Human Genome Project, and its completion in 2005 with the publication on humans’ genetic code opened the door to new fields of research that relate the genetic endowment of every individual with different clinical characteristics. One of these characteristics is the way to deal with an infectious disease.</p><p id="par0010" class="elsevierStylePara elsevierViewall">An infection involves the entry and multiplication of a microorganism in the tissues of a host, causing a response by the host. In an infectious disease, this response is very important and depends on several factors, including the microbial genome, ultimately responsible for the phenotypic expression of the pathogenic traits of the microorganism, environmental factors and the characteristics inherent to the human subject, codified in their genome.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Throughout history this last factor has been considered less significant, but today it poses a great challenge for genomic medicine.</p><p id="par0015" class="elsevierStylePara elsevierViewall">It is frequent to genotype microorganisms to know their phylogenetic relationships, to perform a more reliable taxonomic identification or to determine their resistance to antibiotics and chemotherapeutics. However, how is human genetics involved in the susceptibility to infections, clinical evolution or response to their treatment? This is a very complex field and currently under development, since human response to common infections is usually due to a highly polygenic inheritance.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Despite this, their research and study seems important, since infectious diseases are responsible for nearly 30% of deaths worldwide<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> and there are many examples of interindividual variability in responses to these diseases.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The suspected existence of a genetic component in the susceptibility to infections is not so recent. Robert Koch, before discovering the tubercle bacillus in 1882, when he noticed the disease in several members of the same family, suspected it might be a genetic disease.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> However, the discovery of <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span> and its association with tuberculosis made the potential genetic hypothesis to be forgotten.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Natural selection exerted by infectious diseases</span><p id="par0025" class="elsevierStylePara elsevierViewall">Throughout the twentieth century, in the study of the clinical course of infections, the human genetic factor regained importance. On the one hand, identical responses were observed against the same infection in twins, in contrast to the high variability existing in the general population to the same clinical case.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> On the other hand, the development of Darwinian evolution theory also shed light on this. The natural selection exerted by pathogenic microorganisms from the dawn of evolution to date has made infectious microorganisms main cause of disease and death throughout human history, not as deadly as when introduced for the first time in a community. This phenomenon became clear during the Spanish and Anglo-Saxon colonization of the Americas,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> since the arrival of colonists, merchant maritime traffic and the opening to the Old World had dramatic consequences on native American Indians. The introduction of infectious diseases from the European continent into populations that had never been in contact with their causal agents caused more deaths than the armed conflicts. Smallpox, influenza, measles, rubella, and tuberculosis were, among others, diseases exported to the American empires, causing a significant natural selection on their populations.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Something similar occurs in West Africa, where important clinical, physiological and immunological differences between ethnic groups have been reported regarding infection, morbidity and prevalence rates of the various plasmodium species.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> The coexistence of Africans with disease from the earliest hominids to date has eased the selection of genetic traits that confer resistance to the disease<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>: sickle cell anemia, thalassemia, glucose-6-phosphate dehydrogenase deficiency or loss of Duffy erythrocyte antigen (necessary for the invasion of <span class="elsevierStyleItalic">Plasmodium vivax</span>), among others.</p><p id="par0035" class="elsevierStylePara elsevierViewall">There are many other examples of natural selection in humans by infectious microorganisms, some of them relatively recent. For example, in the Lübeck disaster in 1929, 69% of 251 German children vaccinated with a batch of <span class="elsevierStyleItalic">Calmette-Guérin</span> bacillus contaminated with <span class="elsevierStyleItalic">M. tuberculosis</span>, survived tuberculosis infection and 9% of them never had a single symptom.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> However, the tubercle bacillus was highly lethal on Native American Indians who were exposed to the bacteria for the first time in the mid-twentieth century, which is estimated to be 90%.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> It is clear that the microorganism is a determining factor, but alone it does not explain so many differences in susceptibility between both groups.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Genetic susceptibility to infectious diseases</span><p id="par0040" class="elsevierStylePara elsevierViewall">There are situations where the link between human genetics and susceptibility to infection has been clearly demonstrated. An example is primary immunodeficiencies, conditions where abnormalities in a single gene increase the likelihood of multiple infections. Proof of these are the mutations in ATM and ADA genes, causing ataxia telangiectasia and severe congenital immunodeficiency, respectively in their carriers. It is also known that some variants in the genes encoding the HLA system or cellular mediators such as TNF-α, IFN-γ and interleukins increase the risk of serious infection, since the mechanisms of immune response of the organism are damaged4.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> However, linking a particular infectious disease to a particular gene is a much more arduous and, for the moment, impractical task, given the high number of genes normally involved in susceptibility. This causes a significant difficulty in discerning between genetic risk and environmental risk, becoming one of the current challenges in biomedical research. In spite of this, in the last years variants have been found in main genes of susceptibility to many common infections.</p><p id="par0045" class="elsevierStylePara elsevierViewall">One of the best known examples is the Δ32 variant of the gene encoding the CCR5 receptor, used by the human immunodeficiency virus (HIV) as a co-receptor for entering lymphocytes and macrophages. Individuals carrying this variant have a nonfunctional CCR5 receptor, to which HIV is unable to bind, resulting in resistance to HIV infection in homozygous carriers and a late progression to acquired immunodeficiency syndrome (AIDS) in heterozygous carriers. Years ago it was proved that an HIV-infected leukemic patient, receiving a bone marrow transplant from a homozygous donor for the CCR5-Δ32 trait, had undetectable levels of HIV.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> These findings promoted the development of a new therapeutic strategy in HIV infection, thus synthesizing maraviroc, the first drug used in CCR5 receptor antagonist that blocks the virus entry into the target cell.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> Thus, the study of human genetics can help us to better understand the pathophysiology of infections and, therefore, to develop new molecules against new therapeutic targets.</p><p id="par0050" class="elsevierStylePara elsevierViewall">It has been hypothesized that the Δ32 variant of CCR5 gene, more prevailing in Caucasians (10%) and practically absent in the rest of the races, might have been favored by natural selection during the smallpox epidemics that decimated Europe during the Middle Ages.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Something similar happens with the Norwalk virus, which causes outbreaks of viral diarrhea. Homozygous individuals with a genetic variant in the α1,2-fucosyltransferase gene – FUT2 – do not express the oligosaccharide that acts as a virus ligand. Therefore, they do not develop the disease.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> The same genetic-molecular mechanism has the natural resistance to parvovirus B19, which causes sudden exanthema or fifth disease, since in the absence of the erythrocyte P-antigen by genetic predisposition, the virus cannot enter the cells.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The study of human genetics has occasionally resulted in surprising findings providing evidence of the arbitrariness in Nature. Thus, a lower susceptibility to Ebola hemorrhagic fever has been reported in individuals with Niemann-Pick disease, a rare genetic disease where the NPC1 receptor is mutated, necessary for the entry of the virus into the target cell.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> As above-mentioned for HIV infection, in Ebola virus infection this finding enabled NPC1 receptor antagonist molecules to be tested as potential therapies. The usefulness of these compounds was demonstrated <span class="elsevierStyleItalic">in vitro</span>, since they blocked the entry of Ebola virus into the cells.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> It is likely that in the geographic areas affected by the last Ebola epidemic of 2014, individuals carrying the mutation in NPC1 may have been selected, given the magnitude of the epidemic outbreak and the rarity of the disease, whose estimated prevalence is 1:150,000 people in Western Europe.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> However, further studies are needed in this field to prove this theory.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Usefulness of genome-wide association studies in finding the variants involved in susceptibility</span><p id="par0065" class="elsevierStylePara elsevierViewall">Advances in molecular biology techniques have helped associate common infectious diseases to a major gene through genome-wide association studies (GWAS). In these tests, the most common genetic variants are studied in different individuals to find out if any of them is associated with any particular trait. GWAS have been typically focused on the study of SNPs (single nucleotide polymorphism), and their function is to discriminate whether for a certain genetic variant there are different allele frequencies among healthy or non-susceptible and non-healthy individuals.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Two gene variants have been found through GWAS that modify susceptibility to disease by dengue virus in humans. On the one hand, in <span class="elsevierStyleItalic">FcγRIIa</span>, which encodes for a gammaglobulin receptor used by the virus to enter the cell and also acts as an activator of phagocytic mechanisms. On the other hand, in VDR, which encodes for the vitamin D receptor, which activates the macrophages in charge of phagocytizing viruses.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The different susceptibility of individuals to bacterial infections led the GWAS studies to search for variants in genes that regulate the innate immune response. The results were very varied. We found an association between many variants of the NOD2 gene (involved in cell signaling pathways) and the predisposition to <span class="elsevierStyleItalic">Mycobacterium leprae</span> infection.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> In the case of meningococcal disease, a variant of the gene encoding for complement factor H was associated with protection against the disease.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> And in invasive pneumococcal infection, susceptibility of individuals was found to be associated with the mannose-binding lectin protein encoded by the MBL gene.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> There are, on the other hand, several genes modulating the bactericidal action of macrophages, whose inactivation results in phagolysosomes incapable of lysis of <span class="elsevierStyleItalic">M. tuberculosis</span>. One of the best known is the SLC11A1 gene. Its abnormalities affect the innate bactericidal function of the reticuloendothelial system. Thus, macrophages act as niches or reservoirs for <span class="elsevierStyleItalic">M. tuberculosis</span> and subjects carrying these genetic disorders become potential best carriers of the tubercle bacillus.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Influence of human genetics on the response to treatment of infections</span><p id="par0080" class="elsevierStylePara elsevierViewall">The study of human genetics allows, in certain infections, to provide a therapeutic profile for the patients or modify the already existing profile. There is evidence to determine the presence of genetic variants that can predict the response to the treatment of infections or its adverse reactions. The rs12979860 polymorphism in the IL28B gene predicted whether treatment-naïve patients with hepatitis C with moderate liver fibrosis and infected with viral genotypes 1 and 4 would respond to standard pegylated interferon and ribavirin combined therapy. Thus, the homozygous carriers of the C allele responded better to this therapy than the T allele carriers, who required the addition of a protease inhibitor to obtain an effective treatment.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Fortunately, these therapies are not currently being used due to the emergence of new direct-acting antivirals. On the other hand, the spontaneous clearance of the virus is higher in homozygous C carriers, resulting in the delay or absence of clinical progression to cirrhosis and carcinoma.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Another example of genetic analysis for therapeutic application is the determination of the HLA-B*5701 variant in HIV-infected individuals. Patients with this variant will be at high risk of being hypersensitive to abacavir antiretroviral, making it impossible to administer such treatment which, in combination with other antiretrovirals, is one of the key therapies in the treatment of the disease. As with HCV and rs12979860 polymorphism, this HLA-B*5701 variant causes a slow and late progression to AIDS in HIV-infected patients.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Influence of human genetics on the progression of infection</span><p id="par0090" class="elsevierStylePara elsevierViewall">The presence of certain human genetic factors may also provide information on the severity or progression of infection. A very striking example is the inactivating mutations of the human EVER-1 and EVER-2 genes, which cause abnormal susceptibility to some human papillomavirus (HPV) genotypes, including HPV5 and HPV8. Such mutations produce impaired cellular immunity, disabling recognition and rejection of HPV antigen-presenting keratinocytes. Thus, Epidermodysplasia verrucciform (known as tree man syndrome) occurs in homozygous patients, a disease consisting of a chronic HPV infection with the emergence of hyperkeratosis and high risk of skin cancer.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="par0095" class="elsevierStylePara elsevierViewall">In an environment of continuous interrelation between man and pathogenic microorganisms, it seems important to study the human factors responsible for a higher susceptibility to certain infectious diseases. Although such susceptibility to infections depends on multiple factors, tools are being developed to relate different genetic variants with certain traits that may be related not only to the tendency to suffer from a particular infectious disease, but also to the progression or response to its treatment. Some examples of recent findings of human infection-related genes, both by viruses and by prions, bacteria or parasites, are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">In the new era of evidence-based medicine, we try to predict the potential consequences that the same infection can have on different patients depending on their individual characteristics. Thus, the study of human host's genetics becomes significant in the study of infectious diseases, added to their etiological diagnosis and providing a beneficial synergy for their understanding, treatment and evolution.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Regarding the title of this article, it is concluded that human genetics can indeed predict the risk of any infectious disease. In certain cases, such as in malaria or HIV, there is already scientific evidence on which genetic variants confer resistance to infection. However, genomics still has decades of research ahead where laboratories will be essential to advance in this field. The line separating the various branches of science, such as genetics, microbiology or immunology, is increasingly narrower, and the collaboration of laboratories in biomedical research is necessary for the progress of medicine.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors report no conflict of interest regarding the contents of this article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Natural selection exerted by infectious diseases" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Genetic susceptibility to infectious diseases" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Usefulness of genome-wide association studies in finding the variants involved in susceptibility" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Influence of human genetics on the response to treatment of infections" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Influence of human genetics on the progression of infection" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-02-24" "fechaAceptado" => "2017-03-14" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Moreno Mayordomo R, López Ramos I, Ortiz de Lejarazu Leonardo R. Capacidad de la genética humana de predecir el riesgo de presentar una enfermedad infecciosa. Med Clin (Barc). 2017;149:32–35.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Infectious microorganism \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Human gene \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Implication \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">References \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Virus</span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Human immunodeficiency virus</td><td class="td" title="table-entry " align="left" valign="top">CCR5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Resistance to infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">De Silva et Stumpf<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a>, 2004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">HLA-B</td><td class="td" title="table-entry " align="left" valign="top">Progression of disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Jose et al.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a>, 2013</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Response to treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hepatitis C virus</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">IL28B</td><td class="td" title="table-entry " align="left" valign="top">Response to treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tanaka et al.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a>, 2009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progression of disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thomas et al.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a>, 2009 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="5" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hepatitis B virus</td><td class="td" title="table-entry " align="left" valign="top">HLA-B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Effectiveness of the vaccine</td><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Godkin et al.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a>, 2005</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-DR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-DQ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-DQ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Differences in susceptibility</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Mbarek et al.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a>, 2011</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-DP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Human papillomavirus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EVER-1/2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Orth<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>, 2010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ebola</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">NPC1</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Resistance to infection</td><td class="td" title="table-entry " align="left" valign="top">Carette et al.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>, 2011 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Côté et al.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>, 2011 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Norwalk virus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FUT2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Resistance to infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lindesmith et al.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a>, 2003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Parvovirus B19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">P1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Resistance to infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brown et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a>, 1994 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dengue</td><td class="td" title="table-entry " align="left" valign="top">FcγRIIa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Progression of disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Fang et al.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a>, 2012</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">VDR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Prions</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creutzfeldt-Jakob \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PRNP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Palmer et al.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>, 1991 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Bacteria</span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mycobacterium tuberculosis</span></td><td class="td" title="table-entry " align="left" valign="top">SLC11A1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Li et al.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>, 2011 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TLR1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ocejo-Vinyals et al.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>, 2013 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mycobacterium leprae</span></td><td class="td" title="table-entry " align="left" valign="top">NOD2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Differences in susceptibility</td><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Zhang et al.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>, 2009</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HLA-DR/DQ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TLR1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">MBL2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Roy et al.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>, 2002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Neisseria meningitidis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CFH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Differences in susceptibility \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Davila et al.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>, 2010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Parasites</span></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Plasmodium</span> sp.</td><td class="td" title="table-entry " align="left" valign="top">G6PDH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Differences in susceptibility</td><td class="td" title="table-entry " align="left" valign="top">Machado et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>, 2010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Modiano et al.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>, 1996 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Plasmodium falciparum</span></td><td class="td" title="table-entry " align="left" valign="top">SLC4A1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Differences in susceptibility</td><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Machado et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>, 2010</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ABO \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Plasmodium vivax</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">DARC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Resistance to infection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Machado et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a>, 2010 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1472649.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Relevant infections whose clinical course is influenced by human genetics.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human genetics of infectious diseases: between proof of principle and paradigm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Alcaïs" 1 => "L. Abel" 2 => "J.L. Casanova" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI38111" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2009" "volumen" => "119" "paginaInicial" => "2506" "paginaFinal" => "2514" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19729848" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <span class="elsevierStyleInterRef" id="intr0010" href="http://www.who.int/gho/mortality_burden_disease/global_burden_disease_DTH6_2008.xls">http://www.who.int/gho/mortality_burden_disease/global_burden_disease_DTH6_2008.xls</span> [accessed 8.11.16]" "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Causes of death 2008: Summary tables" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2011" "editorial" => "World Health Organization" "editorialLocalizacion" => "Geneva, Switzerland" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Desde las fuerzas mágicas hasta Robert Koch: un enfoque epidemiológico de la tuberculosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L. Moreno Altamirano" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Inst Nal Enf Resp Mex" "fecha" => "2004" "volumen" => "17" "paginaInicial" => "117" "paginaFinal" => "125" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bases genéticas de la susceptibilidad a enfermedades infecciosas humanas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.D. Ramírez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Inst Nac Hig" "fecha" => "2007" "volumen" => "38" "paginaInicial" => "43" "paginaFinal" => "54" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Born to die: disease and new world conquest, 1492–1650" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.B. Risse" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Hist 2000" "fecha" => "2000" "volumen" => "44" "paginaInicial" => "118" "paginaFinal" => "120" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Modiano" 1 => "V. Petrarca" 2 => "B.S. Sirima" 3 => "I. Nebié" 4 => "D. Diallo" 5 => "F. Esposito" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "1996" "volumen" => "93" "paginaInicial" => "13206" "paginaFinal" => "13211" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8917569" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "La contribución de los polimorfismos humanos del eritrocito en la protección contra la malaria" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Machado" 1 => "C. Mendes" 2 => "V.E. do Rosário" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Pan-Amaz Saude" "fecha" => "2010" "volumen" => "1" "paginaInicial" => "85" "paginaFinal" => "96" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis in newborns: the lessons of the “Lübeck Disaster” (1929–1933)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G.J. Fox" 1 => "M. Orlova" 2 => "E. Schurr" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.ppat.1005271" "Revista" => array:5 [ "tituloSerie" => "PLoS Pathog" "fecha" => "2016" "volumen" => "12" "paginaInicial" => "e1005271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26794678" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HIV and the CCR5-Delta32 resistance allele" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. De Silva" 1 => "M. Stumpf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.femsle.2004.09.040" "Revista" => array:7 [ "tituloSerie" => "FEMS Microbiol Lett" "fecha" => "2004" "volumen" => "241" "paginaInicial" => "1" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15556703" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283808011664" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CCR5: from natural resistance to a new anti-HIV strategy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "L. Lopalco" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/v2020574" "Revista" => array:6 [ "tituloSerie" => "Viruses" "fecha" => "2010" "volumen" => "2" "paginaInicial" => "574" "paginaFinal" => "600" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21994649" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.P. Galvani" 1 => "M. Slatkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.2435085100" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2003" "volumen" => "100" "paginaInicial" => "15276" "paginaFinal" => "15279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14645720" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human susceptibility and resistance to Norwalk virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Lindesmith" 1 => "C. Moe" 2 => "S. Marionneau" 3 => "N. Ruvoen" 4 => "X. Jiang" 5 => "L. Lindblad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nm860" "Revista" => array:6 [ "tituloSerie" => "Nat Med" "fecha" => "2003" "volumen" => "9" "paginaInicial" => "548" "paginaFinal" => "553" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12692541" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.E. Brown" 1 => "J.R. Hibbs" 2 => "G. Gallinella" 3 => "S.M. Anderson" 4 => "E.D. Lehman" 5 => "P. McCarthy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199404283301704" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1994" "volumen" => "330" "paginaInicial" => "1192" "paginaFinal" => "1196" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8139629" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ebola virus entry requires the cholesterol transporter Niemann Pick C1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.E. Carette" 1 => "M. Raaben" 2 => "A.C. Wong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature10348" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2011" "volumen" => "477" "paginaInicial" => "340" "paginaFinal" => "343" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21866103" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Small molecule inhibitors reveal Niemann Pick C1 is essential for Ebola virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Côté" 1 => "J. Misasi" 2 => "T. Ren" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature10380" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2011" "volumen" => "477" "paginaInicial" => "344" "paginaFinal" => "348" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21866101" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <span class="elsevierStyleInterRef" id="intr0015" href="https://www.ncbi.nlm.nih.gov/books/NBK1296/">https://www.ncbi.nlm.nih.gov/books/NBK1296/</span> [accessed 21.11.16]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Niemann-Pick disease type C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Patterson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2007" "editorial" => "GeneReviews" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chapter 11: genome wide association studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.S. Bush" 1 => "J.H. Moore" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pcbi.1002822" "Revista" => array:5 [ "tituloSerie" => "PLoS Comput Biol" "fecha" => "2012" "volumen" => "8" "paginaInicial" => "e1002822" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23300413" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic polymorphisms of molecules involved in host immune response to dengue virus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "X. Fang" 1 => "Z. Hu" 2 => "W. Shang" 3 => "J. Zhu" 4 => "C. Xu" 5 => "X. Rao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1574-695X.2012.00995.x" "Revista" => array:6 [ "tituloSerie" => "FEMS Immunol Med Microbiol" "fecha" => "2012" "volumen" => "66" "paginaInicial" => "134" "paginaFinal" => "146" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22624675" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genomewide association study of leprosy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.R. Zhang" 1 => "W. Huang" 2 => "S.M. Chen" 3 => "L.D. Sun" 4 => "H. Liu" 5 => "Y. Li" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0903753" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med" "fecha" => "2009" "volumen" => "361" "paginaInicial" => "2609" "paginaFinal" => "2618" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20018961" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022534707024986" "estado" => "S300" "issn" => "00225347" ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genome wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Davila" 1 => "V.J. Wright" 2 => "C.C. Khor" 3 => "K.S. Sim" 4 => "A. Binder" 5 => "W.B. Breunis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.640" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2010" "volumen" => "42" "paginaInicial" => "772" "paginaFinal" => "776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20694013" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MBL genotype and risk of invasive pneumococcal disease: a case control study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Roy" 1 => "K. Knox" 2 => "S. Segal" 3 => "D. Griffiths" 4 => "C.E. Moore" 5 => "K.I. Welsh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(02)08516-1" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2002" "volumen" => "359" "paginaInicial" => "1569" "paginaFinal" => "1573" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12047967" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283809002449" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SLC11A1 (NRAMP1) polymorphisms and tuberculosis susceptibility: updated systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Li" 1 => "Y. Yang" 2 => "F. Zhou" 3 => "Y. Zhang" 4 => "H. Lu" 5 => "Q. Jin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0015831" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e15831" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21283567" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Tanaka" 1 => "N. Nishida" 2 => "M. Suyigama" 3 => "M. Kurosaki" 4 => "K. Matsuura" 5 => "N. Sakamoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.449" "Revista" => array:7 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "1105" "paginaFinal" => "1109" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19749757" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S030228380800626X" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic variation in IL28B and spontaneous clearance of HCV" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.L. Thomas" 1 => "C.L. Thio" 2 => "M.P. Martin" 3 => "Y. Qi" 4 => "D. Ge" 5 => "C. O’hUigin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature08463" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2009" "volumen" => "461" "paginaInicial" => "798" "paginaFinal" => "801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19759533" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HLA B*5701 status, disease progression, and response to antiretroviral therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Jose" 1 => "D. Chadwick" 2 => "T. Hill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.aids.0000432613.95455.71" "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "2013" "volumen" => "27" "paginaInicial" => "2587" "paginaFinal" => "2592" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23921616" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular analysis of HLA class <span class="elsevierStyleSmallCaps">ii</span> associations with hepatitis B virus clearance and vaccine nonresponsiveness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Godkin" 1 => "M. Davenport" 2 => "A.V. Hill" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.20716" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2005" "volumen" => "41" "paginaInicial" => "1383" "paginaFinal" => "1390" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15915462" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0285" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Mbarek" 1 => "H. Ochi" 2 => "Y. Urabe" 3 => "V. Kumar" 4 => "M. Kubo" 5 => "N. Hosono" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/hmg/ddr301" "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2011" "volumen" => "20" "paginaInicial" => "3884" "paginaFinal" => "3892" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21750111" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0290" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetics and susceptibility to human papillomaviruses epidermodysplasia verruciformis, a disease model" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G. Orth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Bull Acad Natl Med" "fecha" => "2010" "volumen" => "194" "paginaInicial" => "923" "paginaFinal" => "940" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21513129" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homozygous prion protein genotype predisposes to sporadic Creutzfeldt-Jakob disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.S. Palmer" 1 => "A.J. Dryden" 2 => "J.T. Hughes" 3 => "J. Collinge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/352340a0" "Revista" => array:7 [ "tituloSerie" => "Nature" "fecha" => "1991" "volumen" => "352" "paginaInicial" => "340" "paginaFinal" => "342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1677164" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0302283810000023" "estado" => "S300" "issn" => "03022838" ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0300" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human toll-like receptor 1 T1805G polymorphism and susceptibility to pulmonary tuberculosis in northern Spain" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.G. Ocejo-Vinyals" 1 => "E. Puente de Mateo" 2 => "F. Ausín" 3 => "R. Agüero" 4 => "J.L. Arroyo" 5 => "M. Gutiérrez-Cuadra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5588/ijtld.12.0767" "Revista" => array:6 [ "tituloSerie" => "Int J Tuberc Lung Dis" "fecha" => "2013" "volumen" => "17" "paginaInicial" => "652" "paginaFinal" => "654" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23575331" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014900000001/v1_201707230028/S2387020617303984/v1_201707230028/en/main.assets" "Apartado" => array:4 [ "identificador" => "44145" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014900000001/v1_201707230028/S2387020617303984/v1_201707230028/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020617303984?idApp=UINPBA00004N" ]
