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

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

doi:10.3390/jcm12165384

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

J Clin Med. 2023 Aug 19;12(16):5384. doi: 10.3390/jcm12165384.

Authors

Naoyuki Yamaguchi¹, Takuki Sakaguchi², Hajime Isomoto^{1

2}, Tatsuo Inamine³, Haruka Ueda³, Daisuke Fukuda^{1

4

5}, Ken Ohnita^{1

6}, Tsutomu Kanda^{1

2}, Hiroki Kurumi², Kayoko Matsushima¹, Tatsuro Hirayama³, Kazuo Yashima², Kazuhiro Tsukamoto³

Affiliations

¹ Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biological Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
² Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan.
³ Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
⁴ Department of Surgical Oncology, Nagasaki University Graduate School of Biological Science, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
⁵ Fukuda Yutaka Clinic, 3-5 Hamaguchi-machi, Nagasaki 852-8107, Japan.
⁶ Shunkaikai Inoue Hospital, 6-12 Takara-machi, Nagasaki 850-0045, Japan.

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.

Keywords: ATG12; ATG16L1; SNPs; gastric mucosal atrophy.

Grants and funding

This study was supported by a research grant from the Non-Profit Organization Aimed at Supporting Community Medicine Research in Nagasaki, Japan. The APC was supported by the Course management fees of the Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University.