ABCMdb

PMID: 23340007

Krawczyk M, Miquel JF, Stokes CS, Zuniga S, Hampe J, Mittal B, Lammert F
Genetics of biliary lithiasis from an ethnic perspective.
Clin Res Hepatol Gastroenterol. 2013 Apr;37(2):119-25. doi: 10.1016/j.clinre.2012.09.002. Epub 2013 Jan 20., [PubMed]

Sentences

No. Mutations Sentence Comment

35 ABCG8 p.Asp19His The analysis which encompassed over 2000 cases and 1400 gallstone-free controls, revealed a strong association between gallstone phenotype and the single nucleotide variant p.D19H within the hepatobiliary cholesterol hemitransporter ABCG5/8: carriers of the p.19H variant demonstrated an increased risk of gallbladder stones (OR = 2.2, 95% CI = 1.8-2.6, P = 1.4 &#d7; 10-14 ) [12]. Login to comment 39 ABCG5 p.Gln604Glu ABCG8 p.Asp19His ABCG8 p.Thr400Lys ABCG8 p.Tyr54Cys For this study, common ABCG5 (p.Q604E) and ABCG8 (p.D19H, p.Y54C, p.T400K, p.A632V) variants were selected and the nonparametric linkage (NPL) as well as case-control analyses were performed. Login to comment 43 ABCG8 p.Asp19His The above results were subsequently replicated in other European cohorts from Sweden (OR = 2.5, 95% CI = 1.3-4.8, P = 0.004) [17] and Denmark (OR = 1.9, 95% CI = 1.7-2.1, P < 0.001) [18], which renders the ABCG8 variant p.D19H the common genetic determinant for increased gallstone risk in European populations. Login to comment 47 ABCG8 p.Asp19His This case-control analysis in over 2500 European Europe Native and Hispanic America Asia (India) SLC10A2 26,28 (rs9514089) ABCG8 12,16-18,54-56 (p.D19H) UGT1A1 11,24,25 (Gilbert) FXR 27 (NR1H4_1) CYP7A1 57,59 (c.-204A>C) SLC01B1 11,52 (p.V174A, p.P155T) Figure 1 Venn diagram illustrating common polymorphisms associated with the risk of gallstone formation in European, American and Asian populations. Login to comment 90 ABCG8 p.Asp19His Moreover, we demonstrated that the minor allele frequencies of the ABCG8 p.D19H [12] and the UGT1A1 Gilbert variants [9] were similar to the European population (8.4% and 11.7%, respectively), conditioning a genetic gallstone risk of similar magnitude. Login to comment 108 ABCG8 p.Asp19His In view of recent population-based and genome-wide association studies that highlighted ABCG8 p.D19H as a major gallstone susceptibility variant in Europe and America, we replicated this association in North Indian populations and observed that the heterozygous genotype was significantly more common in gallstone patients (OR = 2.20; 95% CI = 1.1-4.6, P = 0.038) as compared to healthy controls. Login to comment 110 ABCG8 p.Asp19His A significant (P = 0.017) association between the ABCG8 p.D19H variant and an enhanced risk of gallstones (OR = 2.27) was also detected in an Indian study by Siddapuram et al. [55] when comparing 226 gallstone cases and 222 controls [55]. Login to comment 111 ABCG8 p.Asp19His Interestingly, Kuo et al. [56] demonstrated that the ABCG8 p.D19H variant increases the incidence of gallstones in Chinese individuals as well. Login to comment 121 ABCG8 p.Asp19His The statistical approaches above, which calculated the overall risk of developing GSD, suggested that ABCG8 p.D19H, ESR1 IVS1-397C>T and ADRB3 c.190T>C contribute to GSD risk in the Indian population (unpublished data). Login to comment