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"Bässmann, Ingelore"
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A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
2007
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.
Journal Article