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

Buch S.; Schafmayer C.; Volzke, H; Becker C.; Franke, A; von Eller-Eberstein, H; Kluck, C; Bassmann, I; Brosch M; Lammert, F; Miquel, JF; Nervi, F; Wittig, M; Rosskopf, D; Timm, B; et. al.

Abstract

With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries. We performed an association scan of >500,000 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 PCCA = 4.1 × 10-9), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 × 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 × 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. © 2007 Nature Publishing Group.

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Título según WOS: A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
Título según SCOPUS: A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
Título de la Revista: NATURE GENETICS
Volumen: 39
Número: 8
Editorial: NATURE PORTFOLIO
Fecha de publicación: 2007
Página de inicio: 995
Página final: 999
Idioma: English
URL: http://www.nature.com/doifinder/10.1038/ng2101
DOI:

10.1038/ng2101

Notas: ISI, SCOPUS