A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease

作者：Buch Stephan; Schafmayer Clemens; Volzke Henry; Becker Christian; Franke Andre; von Eller Eberstein Huberta; Kluck Christian; Bassmann Ingelore; Brosch Mario; Lammert Frank; Miquel Juan Francisco; Nervi Flavio; Wittig Michael; Rosskopf Dieter; Timm Birgit; Holl Christine; Seeger Marcus; ElSharawy Abdou; Lu Tim; Egberts Jan; Fandrich Fred; Folsch Ulrich R; Krawczak Michael; Schreiber Stefan; Nurnberg Peter; Tepel Jurgen; Hampe Jochen^*

来源：Nature Genetics, 2007, 39(8): 995-999.

DOI：10.1038/ng2101

With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries1,2. We performed an association scan of 4500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value P-CCA = 4.1 x 10(-9)), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 x 10(-7)) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8-2.6, P = 1.4 x 10(-14)) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile.

• 出版日期2007-8
• 单位河北医科大学