Polymorphisms of the DNA methyltransferase 1 associated with reduced risks of Helicobacter pylori infection and increased risks of gastric atrophy

PLoS One. 2012;7(9):e46058. doi: 10.1371/journal.pone.0046058. Epub 2012 Sep 25.

Abstract

Introduction: DNA methyltransferase-1(DNMT1) is an important enzyme in determining genomic methylation patterns in mammalian cells. We investigated the associations between SNPs in the DNMT1 gene and risks of developing H. pylori seropositivity, gastric atrophy and gastric cancer in the Chinese population.

Methods: The study consisted of 447 patients with gastric cancer; 111 patients with gastric atrophy; and 961 healthy controls. Five SNPs, rs10420321, rs16999593, rs8101866, rs8111085 and rs2288349 of the DNMT1 gene were genotyped. Anti-H.pylori IgG was detected by ELISA. Gastric atrophy was screened by the level of serum pepsinogen Ι and II and then confirmed by endoscopy and histopatholgical examinations.

Results: The age- and sex-adjusted OR of H. pylori seropositivity was 0.67 (95%CI: 0.51-0.87) for rs8111085 TC/CC genotypes, significantly lower than the TT genotype in healthy controls. The adjusted OR of H.pylori seropositivity was 0.68 (95%CI: 0.52-0.89) for rs10420321 AG/GG genotypes. In addition, patients carrying rs2228349 AA genotype have a significantly increased risk for H.pylori seropositivity (OR=1.67; 95%CI: 1.02-2.75). Further haplotype analyses also showed that the ATTTG and ATCTA are significantly associated with increased risks in H.pylori infection compared to the GTCCG haplotype (OR=1.38, 95%CI: 1.08-1.77; OR=1.40, 95% CI: 1.09-1.80). The adjusted ORs of 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, but no association was found between SNPs in the DNMT1 gene and risk of developing gastric cancer.

Conclusions: Individuals with rs10420321 GG and rs8111085 CC genotype of the DNMT1 gene were associated with reduced risks for H.pylori infection. On the other hand, higher risks of gastric atrophy were found in the carriers with these two genotypes compared to other genotypes. Our results suggested that SNPs of DNMT1 could be used as genotypic markers for predicting genetic susceptibilities to H.pylori infection and risks in gastric atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • Female
  • Gastritis, Atrophic / epidemiology
  • Gastritis, Atrophic / genetics*
  • Genotyping Techniques
  • Helicobacter Infections / epidemiology
  • Helicobacter Infections / genetics*
  • Helicobacter pylori / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Stomach Neoplasms / genetics

Substances

  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNMT1 protein, human

Grants and funding

This study has been supported by National Natural Science Foundation of China (30940060 and 81072369).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.