Association of PRMT6 genetic polymorphism with Helicobacter pylori-induced gastric mucosal atrophy was found using a...

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.