title: Functional dyspepsia is associated with GNβ3 C825T and CCK-AR T/C polymorphism.
abstract: BACKGROUND
  A polymorphism (C825T) in G-protein β polypeptide-3 (GNβ3) gene alters intracellular signal transduction, which may cause motor or sensory abnormalities in the gastrointestinal tract. Cholecystokinin-A receptor (CCK-AR) gene T/C polymorphism is associated with a defective splicing of the primary transcript of CCK-AR mRNA, which may modulate satiety signal and delay gastric emptying. Therefore, we evaluated the role of these polymorphisms in patients with functional dyspepsia (FD) as compared with healthy controls (HC).
  
  
  METHODS
  A total of 237 consecutive patients with FD (Rome III) and 250 HC were genotyped for GNβ3 C825T and CCK-AR T/C polymorphisms (PCR-RFLP).
  
  
  RESULTS
  Patients with FD [173 (73%) men, age: 38 ± 12 years] were comparable with HC [195 (78%) men, age: 37 ± 12 years] with respect to age and sex. Out of 237 patients, 26 (11%) had epigastric pain syndrome (EPS), 55 (23.2%) had postprandial distress syndrome (PDS), and 156 (65.8%) had EPS-PDS overlap. Among 237 patients with FD, TT genotype (associated with increased intracellular signal transduction) of GNβ3 C825T polymorphism was more common among patients than among HC [26 (11%) vs. 12 (4.8%), P=0.014; odds ratio (OR): 2.47, 95% confidence interval (CI): 1.2-5.1]. CC (variant) genotype of CCK-AR T/C polymorphism was infrequent among patients than among HC [19 (8%) vs. 46 (18.4%), P=0.001; OR: 0.36, 95% CI: 0.19-0.66]. However, these polymorphisms were comparable among patients with different subtypes of FD (P=0.80 and 0.44).
  
  
  CONCLUSIONS
  TT genotype of GNβ3 C825T is more common among patients with FD than among HC, suggesting that increased signal transduction associated with this genotype may be important in its pathophysiology. However, CCK-AR polymorphism is protective against FD.
authors.affiliation: Departments of aGastroenterology bGenetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Singh
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
authors.forename: Uday C
authors.initials: UC
authors.lastname: Ghoshal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004415:Dyspepsia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D065840:Protective Factors; D043886:Receptor, Cholecystokinin A / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: C000595803:GNB3 protein, human; D043886:Receptor, Cholecystokinin A; D020962:Heterotrimeric GTP-Binding Proteins