ABCMdb

PMID: 21039829

Yoon JH, Kuver R, Choi HS
ABCG8 D19H polymorphism: a basis for the genetic prediction of cholesterol gallstone disease.
J Gastroenterol Hepatol. 2010 Nov;25(11):1713-4. doi: 10.1111/j.1440-1746.2010.06484.x., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCG8 p.Asp19His EDITORIALSjgh_6484 1713..1717 ABCG8 D19H polymorphism: A basis for the genetic prediction of cholesterol gallstone disease Jai H Yoon,* Rahul Kuver† and Ho S Choi* *Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea; and † Division of Gastroenterology, University of Washington, Seattle, Washington, USA See article in J. Gastroenterol. Hepatol. 2010; 25: 1758-1762. Login to comment 2 ABCG8 p.Asp19His ABCG8 p.Asp19His Although a common and economically-relevant problem in developed countries, its pathogenesis remains undefined and is the subject of ongoing investigation.1 Cholesterol gallstone disease appears to be influenced by both genetic predisposition and environmental factors,2 and ethnic and geographical differences have indeed been found.3 Currently, there is active investigation regarding cholesterol gallstone susceptibility genes (Lith genes), as these genes have been found not only to be useful in treating gallstone disease, but also in diagnosing a 'prestone` state in patients.4 Recently, as the result of a genome-wide association scan, cholesterol transporter adenosine triphosphate-binding cassette (ABC) G8 was identified as a susceptibility factor for human cholesterol gallstone disease.5 Buch et al.5 showed that single-nucleotide polymorphism (SNP) A-1791411 in ABCG8 encoded the variant rs11887534 (D19H), and that the association of ABCG8 D19H with cholesterol gallstones was present in Germans and Chileans after adjusting for body mass index, sex, and age. Login to comment 3 ABCG8 p.Asp19His The overall odds ratio for gallstone disease among D19H carriers in Germans and Chileans was 2.2 (95% confidence interval [CI]: 1.8-2.6). Login to comment 10 ABCG8 p.Asp19His As mentioned previously, the presence of the D19H mutant allele of the ABCG8 gene is associated with cholesterol gallstones,5 suggesting that the mutated allele might confer more efficient transport of cholesterol into bile, in turn causing cholesterol supersaturation. Login to comment 11 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys Other studies have identified a variety of polymorphisms in ABCG8 (A632V, T400K, D19H, and C54Y) and in ABCG5 (Q604E) that have been linked to baseline plasma cholesterol levels, cholesterol absorption, or responsiveness to dietary intervention. Login to comment 12 ABCG8 p.Asp19His ABCG8 p.Thr400Lys In addition, genetic variations in the ABCG8 gene (D19H and T400K) might increase the risk of gallstone disease in certain populations.9 These sex- and population-specific gene polymorphisms, and the interactions between sex, genes, and diet also need to be considered in studies of polymorphisms of Lith genes. Login to comment 13 ABCG5 p.Gln604Glu ABCG8 p.Asp19His Hubacek et al.10 reported that none of the polymorphisms examined, including ABCG5 Q604E, ABCG8 D19H, and ABCG8 A632V, were related to plasma lipid levels in patients after 'evolutionary`dietary changes from a traditional, high-fat Eastern European diet to a lower-fat diet based on nutritional advice. Login to comment 14 ABCG8 p.Thr400Lys ABCG8 p.Thr400Lys Yet when a subanalysis of male participants was performed, the ABCG8 T400K wild-type allele carriers exhibited a greater decrease in plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) than mutant allele carriers.10 Wang et al.11 suggested that the T400K polymorphism in ABCG8 might be associated with gallstone disease in Chinese males by revealing a possible association between this transporter gene polymorphism and gallstone formation. Login to comment 15 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys Wang et al.11 examined five common polymorphisms in the ABCG5 (Q604E) and ABCG8 (D19H,Y54C, T400K, A632V) genes in 287 patients with gallstone disease. Login to comment 16 ABCG8 p.Thr400Lys The relative risk of gallstone formation was 2.31 (95% CI: 1.12-4.76) for males carrying the K400 allele of ABCG8 T400K. Login to comment 17 ABCG8 p.Asp19His Katsika et al.12 demonstrated that twins carrying a heterozygous or homozygous ABCG8 D19H genotype have a significantly increased risk of gallstone disease. Login to comment 18 ABCG8 p.Asp19His This result confirmed the ABCG8 D19H genotype as a major risk factor for gallstone disease in Swedish twins. Login to comment 19 ABCG8 p.Asp19His ABCG8 p.Asp19His ABCG8 p.Asp19His Additionally, Chen et al. suggested that the D19H polymorphism of ABCG8 could be considered a susceptible gene marker by revealing an increased likelihood of developing high cholesterol and LDL-C with the D19H polymorphism in Taiwanese consuming an ordinary Chinese diet.13 In this issue of Journal of Gastroenterology and Hepatology, Srivastava et al.14 report that the ABCG8 D19H (rs11887534) variant, DH genotype, and H allele increase susceptibility to cholesterol gallstone disease in a north Indian population. Login to comment 20 ABCG8 p.Asp19His They found that the risk of cholesterol gallstone disease due to the ABCG8 D19H variant was more prominent in females. Login to comment 28 ABCG8 p.Asp19His A combination of these factors might lead to gallstone formation if a threshold of susceptibility is reached, since each susceptibility allele only confers a modest increase in risk.17 However, the D19H substitution of the ABCG8 gene resulted in a completely different situation: low serum cholestanol, sitosterol, and campesterol levels, suggesting limited sterol absorption,18 causing cholesterol supersaturation in bile and promoting the formation of cholesterol gallstones. Login to comment 35 ABCG8 p.Asp19His How does the D19H polymorphism of ABCG8 interact with these factors in promoting cholesterol gallstones? Login to comment 36 ABCG8 p.Asp19His In conclusion, the results of the population-specific study reported by Srivastava et al. confirm that the DH genotype and H allele of the ABCG8 D19H polymorphism are associated with a risk of gallstone susceptibility in a north Indian population. Login to comment