Polymorphisms Located in 3'-UTR are Associated with Severity of Atrophy and Methylation Status in the Gastric Mucosa.

This study aimed to clarify the association of polymorphisms (rs4268033, rs3735656, and rs10226620) with the degree of gastric mucosal atrophy and CpG methylation status. A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). A total of 491 subjects were enrolled in this study. Genotypes and methylation status were determined by polymerase chain reaction (PCR)-single-stranded conformation polymorphism and methylation-specific PCR (Fujita Health University, HM18-094). Either rs3735656 or rs10226620, located in the 3'-UTR of , was significantly associated with the severity of gastric mucosal atrophy using a dominant genetic model (odds ratio [OR], 2.10;  = 0.0012, and OR, 1.98;  = 0.0027, respectively). However, using a recessive genetic model, no significant association was found between three polymorphisms and gastric mucosal atrophy. The serum pepsinogen I/II ratio was significantly lower in subjects with minor alleles of rs3735656 and rs10226620 than in subjects with the wild homozygous allele ( = 0.018 and 0.013, respectively). In a subgroup including 400 of the 491 subjects, the CpG of and were methylated in 132 and 112 subjects, respectively. Fifty subjects had both CpG methylations and 206 subjects had neither methylation. When comparing the groups with both and neither methylations, there were no significant associations between three polymorphisms and methylation using a dominant genetic model. However, all polymorphisms investigated in this study (rs4268033, rs3735656, and rs10226620) were significantly associated with methylation in a recessive genetic model (OR, 3.58;  = 0.0071, OR, 4.49;  = 0.0004, and OR, 3.45;  = 0.0027, respectively). Our results indicate that carrying the minor allele of the polymorphisms, particularly when they are located in the 3'-UTR, has a high risk for the severity of gastric mucosal atrophy; furthermore, CpG methylation may develop in subjects with homozygous minor allele of these polymorphisms.