Submitted on June 27, 2007
Revised on November 15, 2007
Accepted on November 15, 2007
Increased expression of LXR
, ABCG5, ABCG8 and SRBI in the liver from normolipidemic nonobese chinese gallstone patients
Zhao-Yan Jiang, Paolo Parini, Gösta Eggertsen, Matthew A Davis, Hai Hu, Guang-Jun Suo, Sheng-Dao Zhang, Lawrence L Rudel, Tian-Quan Han, and Curt Einarsson
Laboratory Medicine, Karolinska Institute, Stockholm 141 86
Corresponding Author: Curt.Einarsson{at}ki.se,
Cholesterol supersaturation of bile is one prerequisite for gallstone formation. In the present study on Chinese patients with gallstones, we investigated if this phenomenon was correlated with the hepatic expression of genes participating in the metabolism of cholesterol and bile acids. Twenty-two non-obese normolipidemic patients (female/male: 11/11) with gallstone were investigated with 13 age and body mass index matched gallstone-free controls (female/male: 10/3). The bile from the gallstone patients had higher cholesterol saturation than the controls. The mRNA levels of ABCG5/ABCG8, and LXRa in the gallstone patients were increased by 51%, 59% and 102% respectively, and significantly correlated with the molar % of biliary cholesterol and cholesterol saturation index. The mRNA and protein levels of the hepatic SRBI were increased, and a significant correlation was found between the protein levels and the cholesterol saturation index. No differences were recorded between the two groups concerning the hepatic synthesis of cholesterol, bile acids and esterification of cholesterol. Our results suggest that upregulation of ABCG5/ABCG8 in gallstone patients - possibly mediated by increased LXRa - may contribute to the cholesterol supersaturation of bile. Our data are consistent with the possibility that increased amounts of biliary cholesterol may originate from plasma HDL cholesterol by enhanced transfer via SRBI.
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