Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337–1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.

Helicobacter pylori infection results in gastric cancer (GC) with gastric mucosal atrophy (GMA). Some single-nucleotide polymorphisms (SNPs) in the prostate stem cell antigen gene (PSCA) are associated with GC and duodenal ulcers. However, the relationship of other identified SNPs in PSCA with these diseases remains unclear. Herein, the association between PSCA SNPs and GMA among 195 Japanese individuals with H. pylori infection was evaluated. The definition of GMA or non-GMA was based on serum pepsinogen levels or endoscopic findings. Five tag PSCA SNPs were analyzed using PCR high-resolution melting curve analysis with nonlabelled probes. The frequencies of alleles and the genotypes of each tag SNP were compared between the GMA and non-GMA groups. Subsequently, a genetic test was performed using associated SNPs as biomarkers to detect patients developing GMA. Two tag PSCA SNPs (rs2920280 and rs2294008) were related to GMA susceptibility. Individuals with the rs2920280 G/G genotype or the rs2294008 T/T genotype in PSCA had 3.5- and 2.1-fold susceptibility to GMA, respectively. In conclusion, SNP rs2920280 is a possible biomarker for detecting individuals developing GMA. PSCA polymorphisms may be useful biomarkers for predicting GMA linked to GC risk and a screening endoscopy strategy to detect GC related to early stage H. pylori associated GMA.

Background: Chronic gastritis caused by Helicobacter pylori (H. pylori) infection can progress to gastric cancer through atrophic gastritis (AG). The risk of gastric cancer increases with the progression of AG. Therefore, investigating the risk factors for the progression of AG is important. Methods: Using the GTEx and GEO databases, we extracted thirty-four candidate genes involved in the progression of AG. Then, with in silico analysis using HaploReg v4.1 and JASPAR (Matrix ID: MA0113.3), we extracted rs1231760 of RGS2 as a key single-nucleotide polymorphism (SNP) that could be involved in the functional change in the candidate gene. A correlation analysis between the selected SNP and AG in 200 H. pylori-positive and 302 H. pylori-negative participants was conducted. For functional analysis of the SNP, a dual-luciferase assay using reporter plasmids with a major or minor allele sequence was carried out. Results: The frequency of the C/C genotype of rs1231760 was higher in the AG group than in the non-AG group (p = 0.0471). Functional analysis showed that the transcriptional activities were higher at the dexamethasone-stimulating C allele than at the others (p < 0.05). Conclusions: The C/C genotype of rs1231760 in RGS2 could be a biomarker of high-risk H. pylori-positive AG because of an increase in RGS2 expression.