G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia.
OBJECTIVE
In patients with functional dyspepsia, altered alpha-adrenoreceptor function and depression are prevalent, features that are linked to a G-protein beta 3 (GNB3) subunit gene polymorphism (C825T). We aimed to assess the association of specific G-protein beta 3 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 B, 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 B, 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 B, 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.
Holtmann
Gerald
G
Gastroenterology and Hepatology, University of Essen, Germany. g.holtmann@uni-essen.de
Siffert
Winfried
W
Haag
Sebastian
S
Mueller
Norbert
N
Langkafel
Mathias
M
Senf
Wolfgang
W
Zotz
Rainer
R
Talley
Nicholas J
NJ
D015746:Abdominal Pain / Q000235:genetics; D000328:Adult; D017398:Alternative Splicing; D001007:Anxiety / Q000175:diagnosis; D003863:Depression / Q000175:diagnosis; D004415:Dyspepsia / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015398:Signal Transduction
C454420:G-protein beta3 subunit; D020962:Heterotrimeric GTP-Binding Proteins