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

被引：265

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 ^{[1
]}

机构：

[1] Univ Hosp Schleswig Holstein, Dept Med 1, D-24105 Kiel, Germany

[2] Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, D-24105 Kiel, Germany

[3] Univ Hosp Schleswig Holstein, POPGEN Biobank, D-24105 Kiel, Germany

[4] Univ Hosp Schleswig Holstein, Dept Gen & Thorac Surg, D-24105 Kiel, Germany

[5] Univ Hosp Greifswald, Inst Community Med, D-17487 Greifswald, Germany

[6] Univ Cologne, Cologne Ctr Genom, D-50674 Cologne, Germany

[7] RZPD German Resource Ctr Genome Res, D-14059 Berlin, Germany

[8] Univ Hosp Bonn, Dept Internal Med 1, D-53105 Bonn, Germany

[9] Pontificia Univ Catolica Chile, Fac Med, Santiago, Chile

[10] Univ Greifswald, Inst Pharmacol, D-17487 Greifswald, Germany

[11] Univ Hosp Schleswig Holstein, Inst Med Stat & Informat, D-24105 Kiel, Germany

[12] Univ Cologne, CMMC, D-50931 Cologne, Germany

来源：

NATURE GENETICS | 2007年 / 39卷 / 08期

关键词：

D O I：

10.1038/ng2101

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：995 / 999

页数：5

共 31 条

[1] Are plasma lipid levels related to ABCG5/ABCG8 polymorphisms?: A preliminary study in siblings with gallstones [J].