title: Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer.
abstract: OBJECTIVE
  Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A (CCK-AR) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK-AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK-AR Pst I polymorphism in gallstone disease with gallbladder cancer.
  
  
  METHODS
  This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
  
  
  RESULTS
  The frequency of the A1A1 genotype of CCK-AR was significantly higher in gallstone patients than healthy individuals (P = 0.008 odds ratio [OR] = 2.25, and 95% confidence interval [CI]:1.2-4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients (P = 0.041, OR = 0.49, and 95% CI: 0.3-0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed.
  
  
  CONCLUSIONS
  The results suggest that the A1A1 genotype of CCK-AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer.
authors.affiliation: Departments of Genetics, Sanjay Gandi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Anvesha
authors.initials: A
authors.lastname: Srivastava
authors.forename: Sachchida Nand
authors.initials: SN
authors.lastname: Pandey
authors.forename: Manjusha
authors.initials: M
authors.lastname: Dixit
authors.forename: Gourdas
authors.initials: G
authors.lastname: Choudhuri
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005706:Gallbladder Neoplasms / Q000150:complications / Q000235:genetics; D042882:Gallstones / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D043886:Receptor, Cholecystokinin A / Q000235:genetics*; D012307:Risk Factors
chemical_list: D043886:Receptor, Cholecystokinin A