Inamine Tatsuo, Kakihara Ami, Tazoe Yuna, Fukuda Daisuke, Yamaguchi Naoyuki, Hirayama Tatsuro, Isomoto Hajime, Tsukamoto Kazuhiro
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan; Organization for Research Promotion, University of the Ryukyus, 1 Senbaru, Nishiraha, Okinawa, 903-0213, Japan.
Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Microb Pathog. 2025 Sep;206:107809. doi: 10.1016/j.micpath.2025.107809. Epub 2025 Jun 14.
Persistent infection with Helicobacter pylori (H. pylori) causes chronic gastric inflammation, gastric mucosal atrophy (GMA), intestinal metaplasia, and finally progression to gastric cancer. Genetic factors associated with GMA have been identified using a genome wide approach or candidate gene approach based on known functions. In this study, data-driven selection of candidate genes was conducted using publicly available databases, not based on known functions.
We hypothesized that the expression levels of some genes in the stomach may vary depending on single nucleotide polymorphisms (SNPs) and may differentially respond to H. pylori infection. Thus, the Gene Expression Omnibus database, which showed differentially expressed genes in response to H. pylori infection, and cis-expression Quantitative Trait Locus data of the stomach from the GTEx Portal were retrieved, and shared genes between the two lists were selected as candidate genes for further study. This study included 195 individuals diagnosed as H. pylori-positive.
Four SNPs in four genes (ADORA2B, ZFAND2A, APOBEC3B, and PRMT6) were selected and examined for association with susceptibility to GMA. Among the SNPs, rs9435441 in PRMT6 was closely associated with GMA in the minor allele dominant model (p = 0.0004, OR = 2.858). This association could be difficult to identify using an approach based on the known function of PRMT6 because there have been no reports showing direct effects or function of the gene on GMA and/or related conditions. Validation using other populations and experiments to reveal the function of the gene is needed in future studies.
幽门螺杆菌（H. pylori）持续感染会导致慢性胃炎症、胃黏膜萎缩（GMA）、肠化生，最终发展为胃癌。已通过全基因组方法或基于已知功能的候选基因方法鉴定了与GMA相关的遗传因素。在本研究中，使用公开可用数据库进行候选基因的数据驱动选择，而非基于已知功能。
我们假设胃中某些基因的表达水平可能因单核苷酸多态性（SNP）而异，并且对幽门螺杆菌感染的反应可能存在差异。因此，检索了显示对幽门螺杆菌感染有差异表达基因的基因表达综合数据库，以及来自GTEx门户的胃的顺式表达数量性状基因座数据，并选择两个列表中的共享基因作为进一步研究的候选基因。本研究纳入了195名被诊断为幽门螺杆菌阳性的个体。
选择了四个基因（ADORA2B、ZFAND2A、APOBEC3B和PRMT6）中的四个SNP，并检测其与GMA易感性的关联。在这些SNP中，PRMT6中的rs9435441在次要等位基因显性模型中与GMA密切相关（p = 0.0004，OR = 2.858）。由于没有报告显示该基因对GMA和/或相关病症有直接影响或功能，因此使用基于PRMT6已知功能的方法可能难以识别这种关联。未来研究需要使用其他人群进行验证并通过实验揭示该基因的功能。
