Homozygous 825T allele of the GNB3 protein influences the susceptibility of Japanese to dyspepsia

The role of genetics in the susceptibility to functional dyspepsia (FD) is not well established. Recently, two different associations were reported between FD and G-protein beta3 (GNB3) subunit gene polymorphism. We aim to clarify the association between GNB3 protein C825T polymorphism and dyspepsia in the Japanese population. Eight-nine dyspeptics and 94 nondyspeptic subjects enrolled in this study. All subjects underwent gastroscopy and patients with significant upper gastrointestinal findings were excluded. Other diseases were also excluded by face-to-face history and physical examination. GNB3 protein C825T polymorphisms were determined by polymerase chain reaction-restriction fragment-length polymorphism. H. pylori infection status was examined by histology or antibody against H. pylori. Nonsignificant correlation was found between GNB3 protein homozygous 825T and unexplained dyspepsia (OR = 1.65, 95% CI: 0.87-3.13). However, among H. pylori-negative subjects, homozygous GNB3 protein 825T significantly increased the risk of dyspepsia (16.7% versus 40.5%; CC versus TT; OR = 5.10, 95% CI: 1.21-21.43, CC versus others; OR = 3.40, 95% CI: 1.16-9.93, respectively). This significant association remained after logistic regression analysis with adjustment for sex and age (CC versus TT; OR = 5.73, 95% CI: 1.27-25.82, CC versus others; OR = 3.08, 95% CI: 1.02-9.25). No significant correlation was found between GNB3 polymorphism and any dyspeptic symptoms. Our data suggest that the homozygous 825T allele of GNB3 protein is associated with dyspepsia in the H. pylori-negative Japanese population. The role of genetics in the development of dyspepsia needs further evaluation.