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A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
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A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
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Journal Article
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
2007
Overview
With an overall prevalence of 10–20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries
1
,
2
. 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 × 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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Aged
/ Animal Genetics and Genomics
/ ATP Binding Cassette Transporter, Sub-Family G, Member 8
/ ATP-Binding Cassette Transporters - genetics
/ ATP-Binding Cassette Transporters - metabolism
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Fundamental and applied biological sciences. Psychology
/ Gastroenterology. Liver. Pancreas. Abdomen
/ Genetic Predisposition to Disease
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genomics
/ Humans
/ letter
/ Liver
/ Liver. Biliary tract. Portal circulation. Exocrine pancreas
