Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis

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.

Role of IL-10 gene polymorphisms in the development of acute pancreatitis

“…Many studies have reported an association between the IL-10 gene polymorphism and the development of inflammation-related diseases such systemic lupus erythematosus, coronary artery disease, peptic ulcer disease, Behçet's disease, lupus nephritis, and leprosy (Cheng et al, 2010;da Silva et al, 2014;Al-Okaily et al, 2015;Alvarado-Arnez et al, 2015;Krasnova et al, 2015;Yang et al, 2015). Cheng et al (2010) reported that IL-10 -819T/C and -592A/C genetic polymorphisms are associated with an increased risk of erosive reflux esophagitis and gastritis.…”

“…Al-Okaily et al (2015) carried out a study with 272 Saudi subjects, and suggest that IL-10 -1082A/G, -819T/C, and -592A/C genetic variations are associated with the risk of Behçet's disease. Alvarado-Arnez et al (2015) conducted a meta-analysis study, and have reported that IL-10 -819T/C is associated with leprosy susceptibility. Krasnova et al (2015) have suggested that the IL-10 gene polymorphism is associated with the severe course of the disease.…”

Association of the interleukin-10 gene -1082A/G genetic polymorphism with risk of ischemic stroke in a Chinese population

“…IL-10 is a pleiotropic cytokine, and a wealth of evidence supports its regulatory role in the pathology process of several kinds of diseases (Alvarado-Arnez et al, 2015;Ghaleh Baghi et al, 2015;Hsu et al, 2015;Khodaeian et al, 2015). In addition, experimental studies indicated that IL-10 expression could maintain the balance between proinflammatory and anti-inflammatory stimuli in the process of cerebrovascular disease.…”

“…The gene encoding IL-10 (IL10) is present on the chromosomal locus 1q31-32, and several genome regions of chromosome 1 (1q21-23, 1q31-32 and 1q42-44) have been observed to be correlated with development of several kinds of diseases, such as diabetes mellitus, peptic ulcer disease, coronary artery disease, leprosy, chronic hepatitis B infection, and oral cancer (Alvarado-Arnez et al, 2015;Ghaleh Baghi et al, 2015;Hsu et al, 2015;Khodaeian et al, 2015;Miftahussurur and Yamaoka, 2015;Yang et al, 2015). The authors of previous researches have reported the correlation of IL10 gene polymorphisms with the ischemic stroke risk; however, the results are inconsistent (Munshi et al, 2010;Sultana et al, 2011;Xie et al, 2013;Qi et al, 2014).…”

Frequency ofTNFA,INFG, andIL10Gene Polymorphisms and Their Association with MalariaVivaxand Genomic Ancestry

“…The production of the IgG, IgA, and IgM isotypes induced by IL-4 is synergistic with IL-10 [38]. However, high levels can contribute to the maintenance of the parasite in the host and can be related to cerebral malaria and high levels of parasitemia [20, 21, 24].…”