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is a pathogen recognition receptor &#40;PRR&#41; and plays a critical role in host immunity&#46; MBL leads to the activation of the complement system&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> This oligomeric protein consists of structural subunits formed by three identical 32&#8239;kD &#40;kilodaltons&#41; polypeptides&#44; each containing a cross-link with the N-terminal region of cysteine&#44; collagen linked to the neck region&#44; and a region of the C-terminal domain that recognizes carbohydrates in microorganisms&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Across multiple lectin domains&#44; carbohydrates such as mannose &#40;six-carbon carbohydrates&#41; are found on the surface of several pathogens&#44; including <span class="elsevierStyleItalic">Trypanosoma cruzi</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleItalic">Plasmodium falciparum</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and <span class="elsevierStyleItalic">Mycobacterium tuberculosis</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> After the recognition of these molecules by lectin&#44; serine proteases are activated to facilitate opsonization &#40;phagocytosis&#41; by macrophages and lysis of the microorganism surface&#46; <a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> The infectious form of <span class="elsevierStyleItalic">Leishmania</span> &#40;promastigote&#41; is characterized by the presence of lipophosphoglycans &#40;LPG&#41; and other molecules such as mannose&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> These components act as pathogen-associated molecular patterns &#40;PAMPs&#41; that are recognized by complement components&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#44;18</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The MBL2 gene is located on chromosome 10 &#40;10q11&#46;2-q21&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Several SNPs have been identified in this gene&#44; which are known for their functional effect on the development of infectious diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a> Functional SNPs&#44; located in the promoter region&#44; such as the -550&#8239;H&#47;L SNP &#40;G&#8239;&#62;&#8239;C substitution&#44; rs11003125&#41;&#44; -221 X&#47;Y &#40;C&#8239;&#62;&#8239;G substitution&#44; rs7096206&#41; and &#43;4 Q&#47;P &#40;C&#8239;&#62;&#8239;T substitution&#44; rs7095891&#41; located in the untranslated region&#44; can regulate the transcription rate of the gene&#46; <a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In the first exon&#44; there are three SNPs located at codon 52 CGT&#8239;&#62;&#8239;TGT &#40;rs5030737&#41;&#44; codon 54 GGC&#8239;&#62;&#8239;GAC &#40;rs1800450&#41; and codon 57 GGA&#8239;&#62;&#8239;GAA &#40;rs1800451&#41;&#44; corresponding to amino acid changes of arginine to cysteine &#8203;&#8203;&#40;Arg52Cys&#44; allele D&#41;&#44; glycine to aspartic acid &#40;Gly54Asp&#44; allele B&#41; and glycine to glutamic acid &#40;Gly57Glu&#44; allele C&#41; in the collagen region of the polypeptide chain&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> These three polymorphisms form the AO system&#44; in which the wild-type allele is described as the A allele and the O allele as a mutant&#46; The A&#47;O genotype is correlated with low levels of the protein and is undetectable for the O&#47;O genotype&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Conflicting results are observed between the MBL2 gene variants and susceptibility to leishmaniasis&#46; Variants featuring high levels of the protein have been associated with susceptibility to VL in Africa&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> northeastern Brazil&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and India&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> However&#44; a study performed in individuals with CL in northern Amazonas&#44; Brazil&#44; showed that all polymorphisms related to low levels of MBL had a strong association with susceptibility&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Some studies have been conducted previously to assess the effects of the MBL2 gene polymorphisms on the evolution of the infection in leishmaniasis&#44; with contradictory results due to the small sample size&#44; which lacks adequate power to detect the effects of MBL2 gene polymorphisms on leishmaniasis&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">To date&#44; no systematic review has been performed on MBL2 gene variants and leishmaniasis&#46; The use of a meta-analysis as a statistical tool to explore risk factors associated with different genetic diseases can provide a reliable conclusion&#46; This systematic review included case-control studies of the genetic association of variants &#40;rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450&#44; and rs1800451&#41; in the MBL2 gene and the risk of developing leishmaniasis&#46; This systematic review is in the International Prospective Register of Systematic Reviews &#40;PROSPERO&#41;&#58; CRD42020201755&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Database search</span><p id="par0040" class="elsevierStylePara elsevierViewall">This systematic review was carried out in accordance with the recommendations of the PRISMA &#40;Preferred Reporting Items for Systematic Reviews and Meta-Analyses&#41; protocol&#46; <a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The PubMed&#44; Science Direct&#44; Cochrane Library&#44; Scopus&#44; and Lilacs databases were searched up to December 2019 by three independent reviewers&#44; with no language or time restrictions&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The following strategy was used&#58; P&#8239;&#61;&#8239;Patients at risk for leishmaniasis&#59; I&#8239;&#61;&#8239;Presence of polymorphisms&#59; C&#8239;&#61;&#8239;Absence of polymorphisms&#59; O&#8239;&#61;&#8239;Occurrence of leishmaniasis&#46; The following terms were used in the search&#58; <span class="elsevierStyleItalic">&#40;&#8220;Leishmaniasis &#8221;OR &#8220;Cutaneous Leishmaniasis&#8221; OR &#8220;Visceral Leishmaniasis &#8220;OR &#8220;Leishmania Infection&#8221; OR &#8220;Leishmania Infections&#8221;&#41; AND &#40;&#8220;Mannose-binding Lectin&#8221; OR &#8220;Mannose-binding Lectin 2&#8221; OR &#8220;MBL&#8221; OR &#8220;MBL2&#8221;&#41; AND &#40;&#8220;Polymorphism&#8221; OR &#8220;Polymorphisms&#8221; OR &#8220;Single Nucleotide Polymorphism&#8221; OR &#8220;Single Nucleotide Polymorphisms&#8221;&#41;</span>&#46; The references cited in eligible articles were manually searched to identify additional publications&#46; Ethical approval and informed consent were not required as this study was based on previously published studies&#44; and there was no direct patient contact or influence on patient care&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Study selection</span><p id="par0050" class="elsevierStylePara elsevierViewall">Two researchers independently evaluated all search results&#46; The inclusion criteria were as follows&#58; 1&#41; Case-control study&#44; 2&#41; rs11003125 &#40;-550&#41;&#44; rs7096206 &#40;-221&#41;&#44; rs7095891 &#40;&#43;4&#41;&#44; rs5030737 &#40;Codon 52&#41;&#44; rs1800450 &#40;CD54&#41; and rs1800451 &#40;CD57&#41; polymorphisms&#44; 3&#41; Studies with sufficiently available genotyping data to calculate the Odds Ratios &#40;OR&#41; with 95&#37; Confidence Intervals &#40;95&#37; CI&#41; and 4&#41; the Hardy-Weinberg Equilibrium &#40;HWE&#41;&#46; The exclusion criteria were&#58; 1&#41; Non-case-control study&#44; 2&#41; Case reports&#44; 3&#41; Reviews&#44; 4&#41; Animal studies&#44; 5&#41; Editorials&#44; 6&#41; Studies with no available data&#44; 7&#41; Studies with meta-analysis&#44; 8&#41; Other polymorphisms and 9&#41; Duplicate data&#46; Subsequently&#44; all selected articles were verified by a third researcher&#44; who resolved the divergences&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Data extraction</span><p id="par0055" class="elsevierStylePara elsevierViewall">Two researchers independently extracted the following data from the included studies&#58; year of publication&#44; first author&#44; study region&#44; ethnic group&#44; clinical form&#44; number of samples&#44; age&#44; and studied SNPs&#46; Disagreements between the researchers were discussed and resolved by consulting a third researcher&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Quality score evaluation</span><p id="par0060" class="elsevierStylePara elsevierViewall">The Newcastle-Ottawa scale &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; was used to assess the quality of the eligible studies&#46; Using this system&#44; each included study was submitted to three judgments&#58; 1&#41; Selection of study groups&#59; 2&#41; Comparability of the groups and 3&#41; Outcome of interest &#40;Case-Control&#41;&#46; Three researchers independently calculated the score for each publication&#46; The scores ranged from 0 to 9&#46; Studies with a score &#62; 6 were considered of high quality&#44; while those with a score &#60; 6 were listed as of low quality&#46; Disagreements between the researchers were discussed in the group and resolved by consensus&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">The meta-analysis evaluated the association of the MBL2 gene and leishmaniasis under the allelic genetic model&#44; -550 &#40;H <span class="elsevierStyleItalic">vs</span>&#46; L&#41;&#44; -221 &#40;X <span class="elsevierStyleItalic">vs</span>&#46; Y&#41;&#44; &#43;4 &#40;Q <span class="elsevierStyleItalic">vs</span>&#46; P&#41;&#44; CD52 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; D&#41;&#44; CD54 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; B&#41;&#44; CD57 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; C&#41; and the A&#47;O genotype &#40;A <span class="elsevierStyleItalic">vs</span>&#46; O&#41;&#46; I<span class="elsevierStyleSup">2</span> was used to assess the heterogeneity between studies&#44; where the values &#8203;&#8203;25&#37;&#44; 50&#37; and 75&#37; corresponded to low&#44; moderate&#44; and high heterogeneity&#44; respectively&#46; The fixed model was used when I<span class="elsevierStyleSup">2</span> &#60; 50&#37;&#44; and the random model was used when I<span class="elsevierStyleSup">2</span> &#62; 50&#37;&#46; Pooled ORs were calculated using the Mantel-Haenszel method&#44; and the statistical significance of OR was determined using Z statistics&#46; In both models&#44; p&#8239;&#61;&#8239;0&#46;005 was considered statistically significant&#46; The RStudio software &#40;<a href="http://www.rstudio.com/products/rstudio/">www&#46;rstudio&#46;com&#47;products&#47;rstudio&#47;</a>&#41;&#44; version 1&#46;3&#46;1 for Windows was used for the statistical analysis of the study&#46; Packages &#40;&#8220;tidyverse&#8221;&#41;&#44; &#40;&#8220;meta&#8221;&#41;&#44; &#40;&#8220;metafor&#8221;&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Characteristics of the included studies</span><p id="par0070" class="elsevierStylePara elsevierViewall">A total of 389 published articles were identified using scientific literature databases &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Among the selected articles&#44; 35 were removed due to duplication&#44; 349 articles were excluded for not meeting the inclusion criteria&#46; Finally&#44; only four articles&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;29</span></a> that met the mandatory criteria&#44; were included in the meta-analysis&#46; These studies were published in English between the years 2007 and 2015 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">One study was conducted on African children&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Two other studies were carried out in mixed populations from the northeastern region of Brazil&#44; consisting of 21&#37; European&#44; 31&#37; African&#44; and 48&#37; Native American descendants&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and from the northern region of Brazil &#40;state of Amazonas&#41;&#44; with a mixed population of 10&#37; African&#44; 40&#37; European&#44; and 50&#37; Native American descendants&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The fourth study was conducted in India but did not specify the ethnicity of the studied subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Three studies analyzed patients with VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;28</span></a> and one analyzed patients with CL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The identified <span class="elsevierStyleItalic">Leishmania spp</span> were&#58; <span class="elsevierStyleItalic">L&#46; chagasi&#44;</span><a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleItalic">L&#46; infantum</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleItalic">L&#46; guyanensis</span><a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> and <span class="elsevierStyleItalic">L&#46; donovani</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> One study analyzed all polymorphisms targeted by this meta-analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> while another analyzed only five SNPs &#40;rs11003125&#44; rs7096206&#44; rs5030737&#44; rs1800450 e rs1800451&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> One study analyzed three SNPs &#40;rs7096206&#44; rs1800450&#44; and rs1800451&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and the remaining study analyzed only one SNP &#40;rs7095891&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Two studies provided sufficient data to perform the A&#47;O system analysis&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;29</span></a> A total of 1758 individuals participated in these studies &#40;791 patients and 967 controls&#41;&#46; According to the Newcastle-Ottawa scale&#44; two studies scored 9 points&#44; and two scored 8 points &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The frequency of genotypes and alleles are organized in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Meta-analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">The results of the meta-analysis are shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46; None of the analyses for any allele genetic model for the two variants &#40;-550 and -221&#41; in the promoter and the &#43;4 variants in the untranslated regions showed any association with susceptibility or resistance to Leishmaniasis &#40;&#8722;550H Allele&#58; OR&#8239;&#61;&#8239;0&#46;92&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;76&#8211;1&#46;12&#59; p&#8239;&#61;&#8239;0&#46;93&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;0&#37; and &#8722;550&#8239;L allele&#58; OR&#8239;&#61;&#8239;1&#46;08&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;89&#8211;1&#46;32&#59; p&#8239;&#61;&#8239;0&#46;93&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;0&#37;&#41;&#44; -221X allele&#58; OR&#8239;&#61;&#8239;0&#46;98&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;45&#8211;2&#46;13&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span> &#61; 91&#37; and -221Y allele&#58; OR&#8239;&#61;&#8239;1&#46;02&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;47&#8211;2&#46;22&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;91&#37;&#41; and Q&#8239;&#43;&#8239;4 allele&#58; OR&#8239;&#61;&#8239;0&#46;85&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;54&#8211;1&#46;33&#59; p&#8239;&#61;&#8239;0&#46;03&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;79&#37; and P allele&#58; OR&#8239;&#61;&#8239;1&#46;17&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;75&#8211;1&#46;84&#59; p&#8239;&#61;&#8239;0&#46;03&#59; I<span class="elsevierStyleSup">2</span> &#61; 79&#37;&#41;&#46; Similar results were obtained for variants located on exon 1 CD52 &#40;allele A of the allele&#58; OR&#8239;&#61;&#8239;1&#46;13&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;68&#8211;1&#46;87&#59; p&#8239;&#61;&#8239;0&#46;87&#59; I<span class="elsevierStyleSup">2</span> &#61; 0&#37; and allele D of the allele&#58; OR&#8239;&#61;&#8239;0&#46;89&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;53&#8211;1&#46;47&#59; p&#8239;&#61;&#8239;0&#46;87&#59; I<span class="elsevierStyleSup">2</span> &#61; 0&#37;&#41;&#44; CD54 &#40;allele A&#58; OR&#8239;&#61;&#8239;1&#46;04&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;62&#8211;1&#46;75&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span> &#61; 79&#37; and allele B&#58; OR&#8239;&#61;&#8239;0&#46;96&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;57&#8211;1&#46;61&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;79&#37;&#41; and CD57 &#40; allele A&#58; OR&#8239;&#61;&#8239;0&#46;85&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;44&#8211;1&#46;62&#59; p&#8239;&#61;&#8239;0&#46;03&#59; I<span class="elsevierStyleSup">2</span> &#61; 72&#37; and allele C&#58; OR&#8239;&#61;&#8239;1&#46;18&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;62&#8211;2&#46;26&#59; p&#8239;&#61;&#8239;0&#46;03&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;72&#37;&#41;&#46; The presence of the wild-type A allele &#40;A allele&#58; OR&#8239;&#61;&#8239;1&#46;05&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;39&#8211;2&#46;81&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;94&#37;&#41; and the mutant O allele &#40;O allele&#58; OR&#8239;&#61;&#8239;0&#46;95&#59; 95&#37; CI&#8239;&#61;&#8239;0&#46;36&#8211;2&#46;56&#59; p&#8239;&#61;&#8239;0&#46;01&#59; I<span class="elsevierStyleSup">2</span>&#8239;&#61;&#8239;94&#37;&#41; were also not associated with susceptibility or resistance&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">MBL recognizes the presence of mannose on the surface of pathogens to promote opsonization and activation of the complement system&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> MBL plays a key role in the innate immune response&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> highlighting its serum concentration as a requirement for predisposition to the development of human infectious diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#44;34</span></a> MBL2 gene variants have been associated with an increased risk of infections caused by protozoa&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#44;36</span></a> However&#44; few studies have investigated genetic variants in the MBL2 gene in Leishmaniasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;29</span></a> Three studies have suggested that variants correlated with low circulating levels of MBL are protective for VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;28</span></a> while one study showed susceptibility to CL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">The conflicting results generated by most studies had weak statistical power due to the small sample size included&#46; To clarify conflicting results in genetic association studies&#44; a meta-analysis offers a powerful method to synthesize data obtained from independent studies&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> To address the limitations of case-control studies&#44; the present meta-analysis was performed to provide statistical evidence of the association between MBL2 gene polymorphisms and susceptibility to leishmaniasis with clustered ORs&#46; To date&#44; this is the first meta-analysis to address the association between the described polymorphisms and leishmaniasis&#46; Previous meta-analyses have suggested an association of polymorphisms in the IL2RA &#40;Interleukin 2 Receptor alpha&#41;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and SLC11A1 &#40;solute carrier family 11 member 1&#41;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> genes with the clinical aspects of leishmaniasis&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In the present study&#44; data from four studies were analyzed according to the low- and high- MBL producing alleles&#46; However&#44; the meta-analysis analyses showed no association between MBL2 gene alleles and susceptibility to leishmaniasis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; High heterogenicity was observed for the variants&#58; -550&#8239;H&#47;L &#40;91&#37;&#41;&#44; &#43;4 Q&#47;P &#40;79&#37;&#41;&#44; CD54 A&#47;B &#40;79&#37;&#41;&#44; CD57 A&#47;C &#40;72&#37;&#41; and A&#47;O &#40;94&#37;&#41;&#46; This can be explained mainly by the ethnic miscegenation of the individuals included in the selected studies&#46; Three studies investigated patients with VL&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;28</span></a> and one patient was investigated with CL&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In each study&#44; the species of the etiologic agent were different&#46; It is important to note that the heterogeneity value influences the adequate statistical model&#46; Studies with small sample sizes can show unreliable results&#46; As a consequence&#44; the random model must always be applied&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Among the selected studies&#44; one analyzed all six target polymorphisms&#44; the diplotypes&#44; and also the haplotypes&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> with high sample size&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">However&#44; caution should be exercised when interpreting these results&#44; as they are based on a few studies&#44; which show divergent results when analyzed separately&#46; Therefore&#44; further studies are needed to confirm whether the variants that determine low serum levels are susceptible or protective&#46; The great importance of the association study involving genetic markers in leishmaniasis is emphasized&#44; aiming at a new understandings of the molecular mechanisms of the disease&#46; The variants can be used as molecular markers of the individual predisposition to certain types of diseases or as therapeutic targets in the development of new drugs&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Overall&#44; this meta-analysis showed no significant association between polymorphisms rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450&#44; and rs1800451 of the MBL2 gene and leishmaniasis&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Financial support</span><p id="par0115" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflicts of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authors&#39; contributions</span><p id="par0125" class="elsevierStylePara elsevierViewall">Wonei de Seixas Vital&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Supervision&#44; Validation&#44; Writing &#8211; review &#38; editing&#46;</p><p id="par1080" class="elsevierStylePara elsevierViewall">Felipe Jules de Ara&#250;jo Santos&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Supervision&#44; Validation&#44; Writing &#8211; review &#38; editing&#46;</p><p id="par1380" class="elsevierStylePara elsevierViewall">Maur&#237;cio Leandro Fernandes Gon&#231;alves&#58; Data curation&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; original draft&#46;</p><p id="par1480" class="elsevierStylePara elsevierViewall">Claudia Dantas Comandolli Wyrepkowski&#58; Data curation&#44; Formal analysis&#44; Methodology&#46;</p><p id="par1586" class="elsevierStylePara elsevierViewall">Rajendranath Ramasawmy&#58; Data curation&#44; Formal analysis&#44; Methodology&#44; Writing &#8211; review &#38; editing&#46;</p><p id="par1580" class="elsevierStylePara elsevierViewall">Silvania da Concei&#231;&#227;o Furtado&#58; Conceptualization&#44; Formal analysis&#44; Methodology&#44; Supervision&#44; Validation&#44; Writing &#8211; review &#38; editing&#46;</p></span></span>"
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    "fechaRecibido" => "2021-06-01"
    "fechaAceptado" => "2021-08-03"
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            1 => "Mannose-binding lectin"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Leishmaniasis is caused by an intracellular protozoan of the <span class="elsevierStyleItalic">Leishmania</span> genus&#46; Mannose-binding lectin &#40;MBL&#41; is a serum complement protein and recognizes lipoprotein antigens in protozoa and the bacterial plasma membrane&#46; Nucleotide variants in the promoter region and exon 1 of the MBL gene can influence its expression or change its molecular structure&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">To evaluate&#44; through a systematic review&#44; case-control studies of the genetic association of variants in the MBL2 gene and the risk of developing leishmaniasis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">This review carried out a search in PubMed&#44; Science Direct&#44; Cochrane Library&#44; Scopus and Lilacs databases for case-control publications with six polymorphisms in the mannose-binding Lectin gene&#46; The following strategy was used&#58; P&#8239;&#61;&#8239;Patients at risk of leishmaniasis&#59; I&#8239;&#61;&#8239;Presence of polymorphisms&#59; C&#8239;&#61;&#8239;Absence of polymorphisms&#59; O&#8239;&#61;&#8239;Occurrence of leishmaniasis&#46; Four case&#47;control studies consisting of 791 patients with leishmaniasis and 967 healthy subjects &#40;Control&#41; are included in this meta-analysis&#46; The association of variants in the mannose-binding Lectin gene and leishmaniasis under the allelic genetic model&#44; -550 &#40;H<span class="elsevierStyleItalic">vs</span>&#46; L&#41;&#44; -221 &#40;X <span class="elsevierStyleItalic">vs</span>&#46; Y&#41;&#44; &#43;4 &#40;Q <span class="elsevierStyleItalic">vs</span>&#46; P&#41;&#44; CD52 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; D&#41;&#44; CD54 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; B&#41;&#44; CD57 &#40;A <span class="elsevierStyleItalic">vs</span>&#46; C&#41; and A&#47;O genotype &#40;A vs&#46; O&#41; was evaluated&#46; International Prospective Register of Systematic Reviews &#40;PROSPERO&#41;&#58; CRD42020201755&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The meta-analysis results for any allelic genetic model showed no significant association for the variants within the promoter&#44; the untranslated region&#44; and exon 1&#44; as well as for the wild-type A allele and mutant allele O with leishmaniasis&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Study limitations</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Caution should be exercised when interpreting these results&#44; as they are based on a few studies&#44; which show divergent results when analyzed separately&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">This meta-analysis showed a non-significant association between the rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450&#44; and rs1800451 polymorphisms of the Mannose-binding Lectin gene and leishmaniasis in any allelic and heterogeneous evaluation&#46;</p></span>"
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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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Selection</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparability</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Outcome</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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Representativeness&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="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Selection of the non-exposed cohort&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">Investigation&nbsp;\t\t\t\t\t\t\n
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                  \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" style="border-bottom: 2px solid black">Final score not present at the start&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comparability &#40;confounding&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Evaluation of outcomes&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Duration&#47;Screening&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Monitoring of adequacy&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Total&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-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Felipe FJ&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salsabil H&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#42;&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2906276.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Newcastle-Ottawa scale of included studies&#46;</p>"
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      ]
      3 => array:8 [
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            "identificador" => "at0020"
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            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">NR&#44; Not Reported&#46;</p>"
          "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="\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" style="border-bottom: 2px solid black">Year&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Country&#47;Region&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ethnic group&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical forms&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Case Control samples</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age&#44; mean years&#8239;&#177;&#8239;SD or mean &#40;range&#41; Case Control</th><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" style="border-bottom: 2px solid black">SNPs&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-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2007&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brazil&#47;Northeast&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mixed&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">61&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">231&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months to 73 years&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 months to 73 years&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs11003125&#44; rs7096206&#44; rs5030737&#44; rs1800450&#44; rs1800451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead rowgroup " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">De Ara&#250;jo FJ</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Brazil&#47; North</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mixed</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CL</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">400</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">382</td><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">311 men &#40;32&#8239;&#177;&#8239;15&#46;5 years&#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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">225 men &#40;38&#8239;&#177;&#8239;17&#46;6 years&#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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs11003125&#44; rs7096206&#44; rs7095891&#44; rs5030737&#44; rs1800450&#44; rs1800451</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="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89 women &#40;32&#8239;&#177;&#8239;13&#46;7&#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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">157 women &#40;34&#8239;&#177;&#8239;17&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2013&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salsabil H&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Morocco&#47;North&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">African&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VL&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">112&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">139&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#8239;&#177;&#8239;12 years&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&#46;5&#8239;&#177;&#8239;12 years&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">rs7096206&#44; rs1800450&#44; rs1800451&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">India&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NR&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VL&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">X</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Salsabiln H&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2013&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">167 &#40;60&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleBold">QP</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">365&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">332&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17 &#40;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">253 &#40;69&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">129 &#40;18&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">601 &#40;82&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">94 &#40;28&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">551 &#40;83&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anshuman M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">218&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">215&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">12 &#40;6&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">de Ara&#250;jo FJ&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2015&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Alonso DP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2007&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Allelic genetic model adopted in the meta-analysis to evaluate the association of MBL2 gene polymorphisms and leishmaniasis&#46;</p>"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Leishmaniose&#58; a review"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "E&#46; Torres-Guerrero"
                            1 => "M&#46;R&#46; Quintanilla-Cedillo"
                            2 => "J&#46; Ruiz-Esmenjaud"
                            3 => "R&#46; Arenas"
                          ]
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                      "titulo" => "Worldwide risk factors in leishmaniasis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Oryan"
                            1 => "M&#46; Akbari"
                          ]
                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.apjtm.2016.06.021"
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                        "tituloSerie" => "Asian Pacific Journal of Tropical Medicine"
                        "fecha" => "2016"
                        "volumen" => "9"
                        "paginaInicial" => "925"
                        "paginaFinal" => "932"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27794384"
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                          "autores" => array:6 [
                            0 => "J&#46; Alvar"
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                            2 => "C&#46; Bern"
                            3 => "M&#46; Herrero"
                            4 => "P&#46; Desjeux"
                            5 => "J&#46; Cano"
                          ]
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                    0 => array:2 [
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23300888"
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