Polymorphism rs7521584 in miR-429 is associated with the severity of atrophic gastritis in patients with Helicobacter pylori infection

摘要

The aim of the present study was to investigate an association of genetic polymorphism (rs7521584) located in miR-200a-200b-429 cluster, which has tumor suppressor and pro-inflammatory function, with the development of gastric mucosal atrophy and metaplasia as a pre-malignant condition. Gastric mucosa samples were obtained from the antrum of 393 patients with no malignancies. The rs7521584 genotype was determined using the polymerase chain reaction-single-strand conformation polymorphism analysis method. The degree of gastritis was assessed histologically in all subjects and serum levels of pepsinogen (PG) I/II were quantified in 123 out of 393 patients. Patients with an atrophy score 1 and metaplasia score 1 were classified into the atrophic gastritis group (AG group). The rs7521584 TT genotype was significantly associated with the development of atrophic gastritis [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.10-5.25; P=0.027), particularly in patients with H. pylori infection (OR, 3.31; 95% CI, 1.35-8.12; P=0.0089). In addition, in patients younger than 60 years of age, this genotype was associated with atrophic gastritis (OR, 3.15; 95% CI 1.03-9.61; P=0.044)]. In patients with H. pylori infection, the metaplasia score was significantly higher in the TT homozygote compared with the GG+GT genotype. In the rs7521584 TT homozygote, serum PG I/II ratio was significantly reduced with increasing age (P=0.0084). No significant trend was identified between the GG+GT genotype and age. The results of the current study indicated that the rs7521584 minor allele homozygote was associated with the development of chronic gastritis under the influence of H. pylori-induced inflammation, particularly with the severity of metaplastic alterations.