ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis

ATG16L1 和 ATG12 基因多态性与萎缩性胃炎的进展有关

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作者:Naoyuki Yamaguchi,Takuki Sakaguchi,Hajime Isomoto,Tatsuo Inamine,Haruka Ueda,Daisuke Fukuda,Ken Ohnita,Tsutomu Kanda,Hiroki Kurumi,Kayoko Matsushima,Tatsuro Hirayama,Kazuo Yashima,Kazuhiro Tsukamoto

Abstract

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.

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