Association of <i>IL10</i> Polymorphisms and Leprosy: A Meta-Analysis

<div><p>Leprosy is a chronic infectious disease that depends on the interplay of several factors. Single nucleotide polymorphisms (SNPs) in host immune related genes have been consistently suggested as participants in susceptibility towards disease. Interleukin-10 (IL-10) is a crucial immunomodulatory cytokine in mycobacterial pathogenesis and especially the -819C>T SNP (rs1800871) has been tested in several case-control studies indicating association with leprosy risk, although a recent consensus estimate is still missing. In this study, we evaluated the association of the -819C>T SNP and leprosy in two new Brazilian family-based populations. Then, we performed meta-analysis for this polymorphism summarizing published studies including these Brazilian family-based groups. Finally, we also retrieved published studies for other distal and proximal <i>IL10</i> polymorphisms: -3575 T>A (rs1800890), -2849 G>A (rs6703630), -2763 C>A (rs6693899), -1082 G>A (rs1800896) and -592 C>A (rs1800872). Results from meta-analysis supported a significant susceptibility association for the -819T allele, with pooled Odds Ratio of 1.22 (CI = 1.11–1.34) and <i>P</i>-value = 3x10^–5 confirming previous data. This result remained unaltered after inclusion of the Brazilian family-based groups (OR = 1.2, CI = 1.10–1.31, <i>P-</i>value = 2x10^–5). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03–1.50, <i>P</i>-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r² = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other <i>IL10</i> polymorphisms analyzed for leprosy outcome. Our results reinforce the role of the -819C>T as a tag SNP (rs1800871) and its association with leprosy susceptibility.</p></div

Characteristics for the Brazilian family-based studies.

<p>Abbreviations: SD, standard deviation; WHO, World Health Organization.</p><p>^a Data is presented as total counts (frequency). The number of subject counts in ethnicity and WHO classification can differ from total individuals due to missing information.</p><p>Characteristics for the Brazilian family-based studies.</p

Forest plots summarizing association of <i>IL10</i> promoter polymorphisms and leprosy.

<p><b>(A)</b> Forest plot for -592 C>A (rs1800872). Five case-control studies were evaluated under random-effects model. Bars represent 95% confidence interval and boxes represent OR values. <b>(B)</b> Forest plot for -819 C>T (rs1800871). Nine case-control studies were evaluated under random-effects model. Bars represent 95% confidence interval and boxes represent OR values.</p

Forest plot for -819 C>T (rs1800871) including Brazilian Family-based data (MG and RJ).

<p>Bars represent 95% confidence interval and boxes represent OR values.</p

Flow diagram of the process of identification of eligible studies.

<p>Flow diagram of the process of identification of eligible studies.</p