Abstract
BackgroundAlthough familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood. Several reports indicate an association between FD and G-protein β3 (GNB3) subunit gene polymorphism (C825T); however, these studies had small sample sizes and the findings are inconclusive. In the present study we clarified the association between GNB3 gene polymorphism and dyspepsia in a large population of Japanese subjects who visited a hospital for annual health check-up.MethodsSubjects with significant upper gastrointestinal findings were excluded. Subjects with dyspeptic symptoms were divided into either a postprandial distress syndrome (PDS) group or an epigastric pain syndrome (EPS) group according to the Rome III criteria. The presence of the GNB3 C825T polymorphism was then evaluated and logistic regression analysis was used to test all variables.ResultsThe GNB3 genotype distribution in subjects without dyspepsia was 191 CC (25.1%), 368 TC (48.4%), and 202 TT (26.5%) and 17 CC (25.0%), 29 TC (42.6%), and 22 TT (32.4%) in subjects with dyspepsia. No significant correlation was found between the GNB3 825TT genotype and dyspepsia. However, the TT genotype was significantly associated with subjects with EPS-like symptoms (odds ratio (OR) = 2.00, 95% confidence interval (CI); 1.07-3.76) compared to the CT/CC genotype adjusted for gender and age. No significant correlation was found between GNB3 polymorphism and PDS-like symptoms (OR = 0.68, 95% CI; 0.31-1.51). With the exclusion of subjects with both EPS- and PDS-like symptoms, only the TT genotype was significantly associated with EPS-like symptoms (OR = 2.73, 95% CI; 1.23-5.91).ConclusionThe homozygous GNB3 825T allele influences the susceptibility to EPS-like dyspepsia.
Highlights
Familial clustering of functional dyspepsia (FD) has been reported, the role of genetics in the susceptibility to FD is still not well understood
As G-proteins play crucial roles as the ligands of G-protein coupling receptor (GPCR), this dysfunction interferes with intracellular signal transduction, and the 825T allele is associated with enhanced G-protein activation [10]
Postprandial distress syndrome (PDS)-like symptoms were defined as postprandial fullness and early satiation, and epigastric pain syndrome (EPS)-like symptoms were defined as epigastric pain and epigastric burning for more than 6 months with symptoms
Summary
Subjects People visiting Healthcare Center of Social Insurance Shiga Hospital for annual health check-up were asked to participate in the study. Differences between GNB3 C825T genotypes and gender, smoking, or drinking were compared by Fisher’s exact test. We compared GNB3 genotypes in subjects with abdominal symptoms vs controls without symptoms, and assessed the association between specific types of symptoms and GNB3 C825T polymorphism. A logistic regression analysis was performed to test the influence of several factors in the association between the GNB3 C825T polymorphism genotype distribution and dyspepsia. Power of the Study In this study, we assessed the potential association of symptoms of dyspepsia with GNB3 C825T allele status. Assuming that approximately 5% of subjects have symptoms of dyspepsia, a 20% increase in the prevalence of a genotype would be of clinical relevance. The actual number of enrolled subjects (68 FD cases and 761 controls) has a power of 93% to detect the assumed difference. For the subgroup analyses for EPS (68 cases), PDS (43 cases), and EPS excluding PDS (28 cases), the power to assumed difference is 79%, 76%, and 61%, respectively
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