Dataset Information

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 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.

SUBMITTER: Alvarado-Arnez LE

PROVIDER: S-EPMC4560376 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.

Alvarado-Arnez Lucia Elena LE Amaral Evaldo P EP Sales-Marques Carolinne C Durães Sandra M B SM Cardoso Cynthia C CC Nunes Sarno Euzenir E Pacheco Antonio G AG Lana Francisco C F FC Moraes Milton Ozório MO

PloS one 20150904 9

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 estim ...[more]

PMID: 26340474

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Project description:BACKGROUND:Recurrent aphthous stomatitis (RAS) is a common oral disease with unknown etiology. The association between IL-6-174?G/C and IL10-1082?G/A polymorphisms and the risk of RAS remains controversial. Therefore, we conducted this meta-analysis to gain more evidence-based information. METHODS:Four online databases, PubMed, Embase, Web of Science, and Cochrane Library, were searched, and the relevant publications were collected. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association of the IL-6-174?G/C and IL10-1082?G/A polymorphisms with RAS susceptibility. RESULTS:Nine published case-control studies with 779 patients and 1016 controls were collected. The overall analysis proved that the IL10-1082?G/A polymorphism was significantly associated with the risk of RAS in a dominant model (GG?+?AG vs AA: OR?=?1.49, 95% CI?=?1.10-2.01, P?=?.01). A subgroup analysis based on ethnicity revealed significant associations in Asian populations in allelic, heterozygote, and dominant models (G vs A: OR?=?1.55, 95% CI?=?1.04-2.31, P?=?.03; AG vs AA: OR?=?1.76, 95% CI?=?1.16-2.67, P?=?.01; GG?+?AG vs AA: OR?=?2.04, 95% CI?=?1.37-3.03, P?=?.00). The association in Caucasians and people of mixed ethnicity requires further study. No significant association was detected between the IL-6-174?G/C polymorphism and RAS in any of the genetic models. However, subgroup analysis by ethnicity revealed that the Caucasians were more likely to develop RAS in 4 genetic models (G vs C: OR?=?2.36, 95% CI?=?1.26-4.41, P?=?.01; GG vs CC: OR?=?7.05, 95% CI?=?3.50-14.18, P?=?.00; GG?+?CG vs CC: OR?=?4.28, 95% CI?=?2.17-8.45, P?=?.00; GG vs CG?+?CC: OR?=?2.59, 95% CI?=?1.05-6.41, P?=?.04). In addition, a significantly decreased risk of RAS susceptibility was found in Asians (CG vs CC: OR?=?0.27, 95% CI?=?0.07-0.99, P?=?.049; GG?+?CG vs CC: OR?=?0.27, 95% CI?=?0.07-0.98, P?=?.047). CONCLUSION:Our meta-analysis indicated that the IL10-1082?G/A polymorphism is associated with RAS susceptibility, especially in Asians. In contrast, the IL-6-174?G/C polymorphism does not have a statistically significant association with RAS susceptibility. However, it may play a different role during the development of RAS in different ethnicities.

Project description:Mannose-binding lectin (MBL) is a serum protein of innate immunity, with a central role in the activation of the complement system through the lectin pathway. This protein is encoded by MBL2 gene, and single-nucleotide polymorphisms located at exon 1, such as rs5030737 C>T (D variant), rs1800450 G>A (B variant), and rs1800451 G>A (C variant), may change the MBL structure and the serum concentration. MBL2 polymorphisms have been associated with several infectious diseases, including leprosy. Host immune response has a major impact on the clinical manifestation of leprosy since only a few individuals infected with Mycobacterium leprae will develop the disease. Therefore, the aim of this study was to evaluate the influence of MBL2 exon 1 polymorphisms (rs5030737, rs1800450, and rs1800451) on the MBL levels and leprosy immunopathogenesis. This case-control study included 350 leprosy patients from Southern Brazil, with 279 classified as multibacillary (MB) and 71 as paucibacillary (PB). The control group consisted of 350 non-consanguineous individuals, who were not diagnosed with leprosy or other infectious and autoimmune diseases. Genotyping was performed by PCR-sequence specific primers, and the MBL serum concentrations were evaluated by ELISA. MBL2 exon 1 polymorphisms were analyzed individually and grouped as genotypes, considering "A" as the wild allele and "O" as the presence of at least one polymorphism (D, B, or C variants). Differences were not observed in the distribution of genotypic and allelic frequencies between leprosy per se patients and controls. However, in a haplotypic analysis, the TGG haplotype presented a risk for development of leprosy per se in women when compared to the wild haplotype (CGG) (OR = 2.69). Comparing patients with MB and PB, in a multivariate analysis, the B variant was associated with the susceptibility of developing the MB form of leprosy (OR = 2.55). Besides that, the CAG haplotype showed an increased susceptibility to develop MB leprosy in women compared to men. It was observed that the A/O genotype in women was associated with a susceptibility to leprosy development per se (OR = 1.66) and progression to MB leprosy (OR = 3.13). In addition, the MBL serum concentrations were in accordance with the genotyping analysis. In summary, our data suggest that MBL2 exon 1 polymorphisms are associated with an increased risk to leprosy development and progression.

Dataset Information

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.

Publications

Association of IL10 Polymorphisms and Leprosy: A Meta-Analysis.

Similar Datasets

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