BACKGROUND AND AIM: 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. METHOD: 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. CONCLUSION: 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.
BACKGROUND AND AIM: 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. METHOD: This study included 165 gallstonepatients, 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 gallstonepatients 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 gallstonepatients 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. CONCLUSION: 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: Rafiq A Shahid; David Q-H Wang; Brian E Fee; Shannon J McCall; Joelle M-J Romac; Steven R Vigna; Rodger A Liddle Journal: Eur J Clin Invest Date: 2015-03 Impact factor: 4.686