Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

• Published in: PloS one Vol. 10; no. 9; p. e0136282
• Main Authors: Alvarado-Arnez, Lucia Elena, Amaral, Evaldo P, Sales-Marques, Carolinne, Durães, Sandra M B, Cardoso, Cynthia C, Nunes Sarno, Euzenir, Pacheco, Antonio G, Lana, Francisco C F, Moraes, Milton Ozório
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-09-2015; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Alleles; Analysis; Brazil; Cytokines; Deoxyribonucleic acid; Development and progression; Disease; DNA; Female; Gene Frequency; Genes; Genetic aspects; Genetic Predisposition to Disease; Genomes; Haplotypes; Humans; Immunity, Innate - genetics; Immunomodulation; Infectious diseases; Interleukin 1; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - immunology; Leprosy; Leprosy - genetics; Leprosy - immunology; Leprosy - pathology; Life assessment; Linkage analysis; Linkage Disequilibrium; Male; Medical ethics; Meta-analysis; Middle Aged; Odds Ratio; Pathogenesis; Patients; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Population; Populations; Promoter Regions, Genetic; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Tuberculosis; Tumor necrosis factor-TNF; Brazil; Rio de Janeiro Brazil; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136282

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 IL10 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 P-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, P-value = 2x10(-5)). Also, meta-analysis confirmed association of -592 A allele and leprosy outcome (OR = 1.24, CI = 1.03-1.50, P-value = 0.02). In support of this, linkage disequilibrium analysis in 1000 genomes AFR, EUR, ASN and AMR populations pointed to r(2) = 1.0 between the -592C>A and -819C>T SNPs. We found no evidence of association for the other IL10 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.