IL10 single nucleotide polymorphisms are related to upregulation of constitutive IL-10 production and susceptibility to Helicobacter pylori infection

Abstract

Background: Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. Materials and Methods: We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4 – 11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5 nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Results: Our results shown that IL10 single nucleotide polymorphisms rs1800896 (OR=1.63; 95% CI =1.11–2.39), rs3024491 (OR=1.71; 95% CI =1.14–2.57), rs1878672 (OR=1.79; 95% CI =1.19–2.68), and rs3024496 (OR=1.48; 95% CI =1.05–2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672,p=.04; rs3024491,p=.01) were strongly associated with infection by Helicobacter pylori. Conclusions: Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti-H. pylori IgG by inducing increased production of IL-10 . Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer.