Abstract
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 r2 = 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.
Highlights
Interleukin-10 (IL-10) is mainly secreted by monocytes and lymphocytes and exhibits an important immunomodulatory activity regulating mainly antibody secretion or inflammation, which if sustained could provoke tissue injury during chronic diseases [1].PLOS ONE | DOI:10.1371/journal.pone.0136282 September 4, 2015Leprosy, caused by intracellular pathogen Mycobacterium leprae, can only progress to active disease in a fraction of infected individuals
P-value 0.97 0.91 (Z = 0.114, P-value = 0.91) family-based populations, we found no evidence of association between leprosy susceptibility and this polymorphism
We found a total of 11 studies that evaluated the influence of IL10 polymorphisms and leprosy published between 2001–2015; all of them were case-control studies that were conducted in Brazilian [7, 18,19,20], Indian [21,22,23], Malawian [24], Mexican [25], Colombian [26] and Chinese [27] populations
Summary
Interleukin-10 (IL-10) is mainly secreted by monocytes and lymphocytes and exhibits an important immunomodulatory activity regulating mainly antibody secretion or inflammation, which if sustained could provoke tissue injury during chronic diseases [1].PLOS ONE | DOI:10.1371/journal.pone.0136282 September 4, 2015Leprosy, caused by intracellular pathogen Mycobacterium leprae, can only progress to active disease in a fraction of infected individuals. Interleukin-10 (IL-10) is mainly secreted by monocytes and lymphocytes and exhibits an important immunomodulatory activity regulating mainly antibody secretion or inflammation, which if sustained could provoke tissue injury during chronic diseases [1]. Leprosy, caused by intracellular pathogen Mycobacterium leprae, can only progress to active disease in a fraction of infected individuals. A sustained IL-10 production, increases phagocytosis in macrophages can drive a permissive anti-microbial programming that leads to intracellular M. leprae replication [2]. CD163+ phagocytic phenotype is positively correlated with higher IL-10 levels in disseminated lepromatous patients [2, 3]. Among exposed household contacts with longer patient exposition a lower ratio of TNF/IL-10 was observed when compared to short term contacts [4]
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