title: A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease.
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 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.
authors.affiliation: First Department of Medicine, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Buch
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Huberta
authors.initials: H
authors.lastname: von Eller-Eberstein
authors.forename: Christian
authors.initials: C
authors.lastname: Kluck
authors.forename: Ingelore
authors.initials: I
authors.lastname: Bässmann
authors.forename: Mario
authors.initials: M
authors.lastname: Brosch
authors.forename: Frank
authors.initials: F
authors.lastname: Lammert
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Miquel
authors.forename: Flavio
authors.initials: F
authors.lastname: Nervi
authors.forename: Michael
authors.initials: M
authors.lastname: Wittig
authors.forename: Dieter
authors.initials: D
authors.lastname: Rosskopf
authors.forename: Birgit
authors.initials: B
authors.lastname: Timm
authors.forename: Christine
authors.initials: C
authors.lastname: Höll
authors.forename: Marcus
authors.initials: M
authors.lastname: Seeger
authors.forename: Abdou
authors.initials: A
authors.lastname: ElSharawy
authors.forename: Tim
authors.initials: T
authors.lastname: Lu
authors.forename: Jan
authors.initials: J
authors.lastname: Egberts
authors.forename: Fred
authors.initials: F
authors.lastname: Fändrich
authors.forename: Ulrich R
authors.initials: UR
authors.lastname: Fölsch
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Jürgen
authors.initials: J
authors.lastname: Tepel
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000235:genetics* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D002784:Cholesterol