Single nucleotide polymorphisms of DNA methyltransferase 1 gene is associated with the risk of gastric atrophy and helicobacter pylori Infection

Abstract

Introduction: DNA methylation in selected gene promoters, are recognized as common molecular alterations in human cancers. In this study, the association of single nucleotide polymorphisms in DNA methyltransferase (DNMT) 1 gene with the risk of H. pylori infection, gastric atrophy, and gastric cancer were investigated in Chinese population. Methods: From 2008 to 2010, 447 gastric cancer, 111 gastric atrophy patients and 961 healthy controls were selected. SNPs rs10420321, rs16999593, rs8101866, rs8111085 and rs2288349 of DNMT1 gene were genotyped by Taqman assay. Gastric atrophy was screened by the levels of serum pepsinogen I and II, confirmed by endoscopy and histopatholgical examinations. Serum anti-H. pylori IgG were detected by ELISA. Results: H. pylori (+) were significantly higher in gastric cancer and gastric atrophy compared to that in control group (69.1% and 75.7% vs. 49.7%, P < 0.001). The OR of H. pylori (+) were significantly reduced with the rs8111085 TC/CC genotypes relative to the TT genotype (OR = 0.67; 95% CI: 0.51-0.87) among controls. The OR of rs10420321 AG/GG genotypes were 0.68 (95% CI: 0.52-0.89). Conversely, rs2228349 AA genotype had a significantly increased risk for H. pylori infection (OR = 1.67; 95% CI: 1.02-2.75). The ORs for gastric atrophy were 1.66 (95% CI: 1.06-2.61) for rs10420321 GG genotype and 1.67 (95% CI 1.06-2.63, P = 0.03) for rs8111085 CC genotype. However, No significant association between five SNPs and the risk of gastric cancer was found. Conclusions: The study indicated that rs8111085, rs10420321 and rs2228349 polymorphisms of DNMT1 gene are significantly associated with H. pylori infection and gastric atrophy in Chinese population, suggesting that the DNMT1 gene polymorphisms could be used as a useful marker of genetic susceptibility to H. pylori infection and gastric atrophy.