Combined Effect of miR-146a rs2910164 G/C Polymorphism and Toll-like Receptor 4 +3725 G/C Polymorphism on the Risk of Severe Gastric Atrophy in Japanese

Abstract

A G/C polymorphism in miRNA-146a (rs2910164) was shown to be associated with the risk of hepatocellular carcinoma. This study aimed to examine the associations of the miR-146a G/C (rs2910164) and TLR4 +3725 G/C (rs11536889) polymorphisms with the risk of Helicobacter pylori (H. pylori) infection, gastric atrophy, and gastric cancer in a Japanese population. Subjects for this study were 583 histologically diagnosed gastric cancer patients and age- and sex-frequency-matched 1,742 control outpatients (1,637 subjects were eligible for the analyses), who visited Aichi Cancer Center Hospital from the year 2001 to 2005. Serum pepsinogens were measured to evaluate gastric atrophy. When H. pylori-seropositive subjects or subjects with gastric atrophy were defined as H. pylori-infected subjects, the age- and sex-adjusted odds ratio (aOR) of severe gastric atrophy among the H. pylori infected was 1.44 (95% confidence interval [95% CI]=0.89-2.34, p=0.133) in G/G genotype of miR-146a polymorphism. When combined with TLR4 G/C polymorphism, the OR in those with miR-146a G/G and TLR4 G/C+C/C genotypes was significantly increased relative to those with miR-146a C/C+G/C and TLR4 G/G among the H. pylori-infected subjects: aOR=2.04 (95% CI=1.10-3.82, p=0.025). This study revealed the combined effect of miR-146a rs2910164 G/G and TLR4 +3725 C allele on the increased risk of severe gastric atrophy among the H. pylori-infected Japanese subjects.