The C/C Genotype of rs1231760 in <i>RGS2</i> Is a Risk Factor for the Progression of <i>H. pylori</i>-Positive Atrophic Gastritis by Increasing <i>RGS2</i> Expression
Naoyuki Yamaguchi,
Takuki Sakaguchi,
Jing-Jing Wei,
Yuna Tazoe,
Tatsuo Inamine,
Daisuke Fukuda,
Ken Ohnita,
Tatsuro Hirayama,
Hajime Isomoto,
Kayoko Matsushima,
Kazuhiro Tsukamoto
Affiliations
Naoyuki Yamaguchi
Department of Gastroenterology and Hepatology, Graduate School of Biological Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Takuki Sakaguchi
Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago 683-8504, Japan
Jing-Jing Wei
Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago 683-8504, Japan
Yuna Tazoe
Department of Pharmacotherapeutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Tatsuo Inamine
Department of Pharmacotherapeutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Daisuke Fukuda
Department of Gastroenterology and Hepatology, Graduate School of Biological Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Ken Ohnita
Department of Gastroenterology and Hepatology, Graduate School of Biological Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Tatsuro Hirayama
Department of Pharmacotherapeutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Hajime Isomoto
Department of Gastroenterology and Nephrology, Faculty of Medicine, Tottori University, 36-1 Nishi-Cho, Yonago 683-8504, Japan
Kayoko Matsushima
Department of Gastroenterology and Hepatology, Graduate School of Biological Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
Kazuhiro Tsukamoto
Department of Pharmacotherapeutics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan
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 RGS2 could be a biomarker of high-risk H. pylori-positive AG because of an increase in RGS2 expression.
