Autophagy-Related Gene ATG7 Polymorphism Could Potentially Serve as a Biomarker of the Progression of Atrophic Gastritis

Author:

Yamaguchi Naoyuki1,Sakaguchi Takuki2,Taira Miki3,Fukuda Daisuke145,Ohnita Ken16ORCID,Hirayama Tatsuro3,Yashima Kazuo2,Isomoto Hajime12,Tsukamoto Kazuhiro3

Affiliation:

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

Cytotoxin-associated gene A (CagA) is an oncoprotein that H. pylori injects into the host’s gastric epithelial cells and that induces proinflammatory cytokines, such as interleukin (IL)-18 and IL-1β. As a result, it leads to atrophic gastritis (AG), a precancerous lesion of gastric cancer. On the other hand, host cells degrade CagA using autophagy systems. However, few studies exist about the single nucleotide polymorphisms (SNPs) in MAP1LC3A, MAP1LC3B, ATG4A, ATG4B, ATG4C, ATG7, and ATG13, which belong to the autophagy-related genes concerning AG. This study aimed to detect biomarkers associated with AG. Herein, H. pylori-positive subjects (n = 200) were divided into the AG (n = 94) and non-AG (n = 106) groups. Thirty tag SNPs were selected from the above seven candidate genes. The SNP frequency between the two groups was analyzed. The frequency of the C/T or T/T genotype at rs4683787 of ATG7 was significantly lower in the AG group than in the non-AG group (p = 0.034, odds ratio = 0.535). Based on multivariate analysis, the C/C genotype of rs4684787 and age were independently associated with gastric mucosal atrophy. This finding helps stratify the patients needing timely endoscopic screening or early eradication of H. pylori.

Funder

Non-Profit Organization Aimed

Publisher

MDPI AG

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