G-protein β3 subunit 825 CC genotype is associated with unexplained (functioncal) dyspepsia

Background & Aims: In patients with functional dyspepsia, altered alpha-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein 03 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein beta3 subunit genotypes with functional dyspepsia. Methods: In study A, abdominal symptoms were assessed in 67 patients with unexplained, upper abdominal symptoms and 259 consecutive blood donors with and without abdominal symptoms. In study 13, a further 56 patients with functional dyspepsia and 112 age- and sex-matched healthy controls from a blood donor population study were evaluated. Genomic DNA was isolated from buccal swabs and genotyping of the C825T polymorphisms was performed by polymerase chain reaction and restriction analysis. Results: In the blood donors with no abdominal symptoms in study A (controls, n = 161), genotype distribution was 17 TT, 77 TC, and 67 CC. In blood donors and patients with unexplained abdominal symptoms, genotype distribution was 22 TT 54 TC, and 89 CC (P = 0.007 vs. controls). In study 13, the genotype distribution in functional dyspepsia patients was 4 TT, :18 CT, and 34 CC compared with 4 TT, 62 CT, and 46 CC in the controls (P < 0.02). Combining studies A and 13, the odds ratio (OR) adjusted for age and sex for upper abdominal symptoms associated with the CC: genotype was 2.2 (95% confidence interval [CI]: 1.4-3.3), compared with subjects with TC and TT genotype carrying an allele. Conclusions: Homozygous GNB3 825C carrier status is associated with unexplained predominantly upper abdominal symptoms.