Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy

Yamaguchi, Naoyuki; Sakaguchi, Takuki; Isomoto, Hajime; Inamine, Tatsuo; Tsukamoto, Ryuta; Fukuda, Daisuke; Ohnita, Ken; Kanda, Tsutomu; Matsushima, Kayoko; Hirayama, Tatsuro; Yashima, Kazuo; Tsukamoto, Kazuhiro

doi:10.1186/s41021-023-00274-5

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…As mentioned in previous reports [18][19][20], 94 participants were divided into the AG group, and the average age of the AG group was older than that of the non-AG group (59.2 ± 9.52 vs. 54.9 ± 10.93, p = 0.002). On the other hand, there was no difference in gender (male/female) (37/57 vs. 50/56, p = 0.266).…”

Section: Clinical Characteristics Of the Subjectsmentioning

confidence: 77%

“…As previously reported [18][19][20], 503 participants who underwent upper gastrointestinal endoscopy at Fukuda Surgical Hospital for their medical checkup were included. Two hundred were diagnosed as H. pylori-positive based on the H. pylori antibody titer.…”

Section: Subjectsmentioning

confidence: 99%

“…After that, we classified the participants into the AG and non-AG groups based on the pepsinogen (PG) method. Specifically, participants with a PG I ≤ 70 and a PG I/II ratio ≤ 3.0 were assigned to the AG group, and those who failed to meet either criterion were assigned to the non-AG group [19]. All of them signed an informed consent form.…”

Section: Subjectsmentioning

confidence: 99%

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

Yamaguchi,

Sakaguchi,

Taira

et al. 2024

JCM

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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.

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Section: Clinical Characteristics Of the Subjectsmentioning

confidence: 77%

Section: Subjectsmentioning

confidence: 99%

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

Yamaguchi,

Sakaguchi,

Taira

et al. 2024

JCM

Self Cite

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“…The subjects were two hundred H. pylori -infected patients ( H. pylori antibody titers ≥ 10 U/mL, E-plate Eiken H. pylori antibody II; Eiken Chemical, Tokyo, Japan) [ 30 ] among five hundred and three patients who underwent esophagogastroduodenoscopy at Fukuda Yutaka Clinic for their health check-up, as previously reported [ 31 ]. Participants who were younger than eighty and had no H. pylori eradication history were included.…”

Section: Methodsmentioning

confidence: 99%

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

Yamaguchi,

Sakaguchi,

Isomoto

et al. 2023

JCM

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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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The C/C Genotype of rs1231760 in RGS2 Is a Risk Factor for the Progression of H. pylori-Positive Atrophic Gastritis by Increasing RGS2 Expression

Yamaguchi,

Sakaguchi,

Wei

et al. 2024

Diagnostics

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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.

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Polymorphism in autophagy-related genes LRP1 and CAPZA1 may promote gastric mucosal atrophy

Cited by 4 publications

References 38 publications

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

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

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

The C/C Genotype of rs1231760 in RGS2 Is a Risk Factor for the Progression of H. pylori-Positive Atrophic Gastritis by Increasing RGS2 Expression

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