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: Roscovitine manufacturer 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. Family, twin and epidemiological studies have confirmed the heritability of symptomatic gallstones.1–4 In general, gallstone susceptibility has been suggested to include the combination of predisposing alleles of multiple lithogenic (LITH) genes selleck screening library and environmental factors.5 Cholesterol type gallstones predominate (> 85%) in the developed world.6 Also in the northern Indian population, the majority of gallstones are cholesterol types, which contain > 50% cholesterol along with small amounts of bile salts, unconjugated
bilirubin, varying amounts of protein and calcium salts.7,8 It is also known that both absorption efficiency and synthesis of cholesterol are genetically determined. In bile, cholesterol is tightly regulated by the interplay of cholesterol absorption, biosynthesis and turnover.9,10 The main cause of cholesterol gallstone formation is considered to result from the supersaturation of bile with cholesterol in the gallbladder. The excretion of cholesterol from the liver is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8, which are typically expressed in hepatocytes, enterocytes and gallbladder epithelial cells.11,12 The ABCG8 gene is located in head-to-head orientation with the ABCG5 gene on chromosome 2p21, between D2S2294 and D2S2298. Genetic analyses showed that despite the close proximity between
these two genes, ABCG8 shows much greater genetic learn more variability in comparison with ABCG5.13,14ABCG8 contains 13 exons and spans approximately 28 kb.15 Linkage and association studies have proposed cholesterol transporter ABCG5/G8 as a potential candidate for the genetic determinant of gallstone formation, or LITH gene.16,17 Buch et al.,18 using genome wide association, identified a single nucleotide polymorphism (SNP) (rs11887534) in the ABCG8 gene, conferring G>C transversion corresponding to asp19-to-his (D19H) substitution, which was significantly associated with gallstone disease. The genetic association studies are population specific and require validation in different populations. Considering the importance of the ABCG8 transporter in maintaining the cholesterol homeostasis and the association of the D19H genetic variant with gallstone disease, we aimed to explore the role of the ABCG8 D19H polymorphism in susceptibility to gallstone disease in a high-risk northern Indian population.