Associations between a PTPN11 Polymorphism and Gastric Atrophy - Opposite in Uzbekistan to that in Japan

Abstract

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interactswith cagA from Helicobacter pylori (H. pylori). Our previous studies found the AA genotype of a G/A singlenucleotide polymorphism at intron 3 (rs2301756) of PTPN11 gene, which encodes SHP-2, to be associated witha lower risk of gastric atrophy. The present study aimed to examine the association with gastric atrophy amongthe subjects of a case-control study of peptic ulcer disease (PUD) conducted in the Uzbek Republic. Cases were95 patients (61 males and 34 females) with PUD aged 16 to 85 years. Controls were 102 hospital volunteers (42males and 60 females) including 42 patients with miscellaneous diseases, aged 15 to 75 years. Gastric atrophywas evaluated with serum pepsinogens (PG1<70ng/ml and PG1/PG2<3). Polymorphisms of PTPN11 at intron 3(rs2301756) and intron10 (rs12229892) were genotyped with PCR with confronting two-pair primers (PCRCTPP).Anti-cagA IgG antibody was detected in 93.7% of cases and 77.5% in controls. Gastric atrophy wasobserved in 24.2% of the PUD patients and 33.3% in the controls. The A allele at intron 3 was completely linkedto the G allele at intron 10. The age, sex, and group (cases and controls) adjusted odds ratio of gastric atrophywas 0.18 (95% confidence interval, 0.04-0.86) for intron 3 GG genotype relative to AA genotype. Since thefinding was opposite to that among Japanese, the H. pylori strains and/or lifestyle in Uzbekistan might modifythe association.