Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.
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.
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Lucia Elena
LE
Alvarado-Arnez
Departamento de Enfermagem Materno-Infantil e Saúde Pública, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Evaldo P
EP
Amaral
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Carolinne
C
Sales-Marques
Departamento de Medicina Clínica, Serviço de Dermatologia da Universidade Federal Fluminense, Rio de Janeiro, Brazil.
Sandra M B
SM
Durães
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Cynthia C
CC
Cardoso
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Euzenir
E
Nunes Sarno
Programa de Computação Científica, Fiocruz, Rio de Janeiro, Brazil.
Antonio G
AG
Pacheco
Departamento de Enfermagem Materno-Infantil e Saúde Pública, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Francisco C F
FC
Lana
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Milton Ozório
MO
Moraes
D000293:Adolescent; D000328:Adult; D000483:Alleles; D001938:Brazil; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007918:Leprosy / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
C508609:IL10 protein, human; D016753:Interleukin-10