J Gastroenterol Hepatol 2010 Nov;25(11):1758-62
Departments of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Background And Aim: The excretion of cholesterol from the liver is regulated by the ATP-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 might be related to the genetic predisposition of gallstone disease, which is causatively related to supersaturation of cholesterol in bile. We aimed to examine the role of the ABCG8 D19H (rs11887534) polymorphism in susceptibility to gallstone disease in the northern Indian population.
Methods: The study included 220 confirmed gallstone patients and 230 controls. Genotyping for the ABCG8 D19H polymorphism was carried out using the PCR-RFLP method.
Results: We observed that the ABCG8 DH genotype frequency was significantly higher in gallstone patients (P = 0.038; odds ratio [OR] = 2.20; 95% confidence interval [CI] = 1.1-4.6). At allele level also, the ABCG8 variant allele conferred an increased risk for gallstone susceptibility (P = 0.043; OR = 2.12; 95% CI = 1.2-4.3). The risk as a result of ABCG8 D19H variation was more pronounced in female gallstone patients at genotype (P = 0.026; OR = 3.01, 95% CI = 1.1-7.9) as well as allele level (P = 0.030; OR = 2.85; 95% CI = 1.1-7.3). However, the molecular modeling results of the rs11887534 polymorphism showed that the overall configuration of both wild-type and polymorphic ABCG8 protein were similar, with negligible deviation at the site of polymorphism.
Conclusion: Carriers of the DH genotype and H allele of the ABCG8 D19H polymorphism harbor a higher risk for gallstone susceptibility in the northern Indian population.