The role of the HLA-DQA1 gene in resistance to atrophic gastritis and gastric adenocarcinoma induced byHelicobacter pylori infection

Abstract

BACKGROUND: It has been suggested that immunogenetic factors for susceptibility or resistance to disease caused by Helicobacter pylori exist in the host. To examine host genetic factors that increase the risk of gastric adenocarcinoma among H. pylori-infected persons, the HLA-DQA1 locus was examined in patients with gastric adenocarcinoma. METHODS: Eighty-two gastric adenocarcinoma patients and 167 unrelated controls were examined for H. pylori infection and HLA-DQA1 genotyping. In addition, serum pepsinogen A (PGA) and pepsinogen C (PGC) values and the PGA/PGC ratio, which have been characterized as markers of gastric mucosal atrophy, also were analyzed. RESULTS: Of the 167 controls, 121 were H. pylori positive (+) and 46 were H. pylori negative (-). All H. pylori (-) individuals had normal endoscopic and histologic findings. Among the 121 H. pylori (+) controls, 36 had superficial gastritis and 85 had atrophic gastritis. The allele frequency of DQA1*0102 was significantly lower in the H. pylori (+) atrophic gastritis group than in the H. pylori (+) superficial gastritis and H. pylori (-) normal control groups. In addition, the allele frequency of DQA1*0102 also was significantly lower in the H. pylori (+) intestinal type gastric adenocarcinoma group than in the H. pylori (-) normal control, H. pylori (+) superficial gastritis, and H. pylori (-) diffuse type gastric adenocarcinoma groups. Serum PGA and PGC values and the PGA/PGC ratio did not differ significantly among HLA-DQA1 genotypes; however, the PGA/PGC ratio was significantly lower in the H. pylori (+) atrophic gastritis and H. pylori (+) intestinal type gastric adenocarcinoma groups than in the H. pylori (-) normal control and H. pylori (+) superficial gastritis groups. CONCLUSIONS: The DQA1*0102 allele may contribute to resistance against H. pylori-associated gastric atrophy and its association with intestinal type gastric adenocarcinoma, whereas the absence of DQA1*0102 may be a host genetic risk factor for H. pylori-associated atrophic gastritis and intestinal type gastric adenocarcinoma.