期刊
HEPATOLOGY RESEARCH
卷 30, 期 2, 页码 91-95出版社
WILEY
DOI: 10.1016/j.hepres.2004.07.005
关键词
organic anion transporter; polymorphism; hepatobiliary transport; pravastatin
To assess the contribution of OATP-C to the hepatobiliary transport of bilirubin, a pharmacogenomic evaluation with regard to polymorphisms of three candidate genes, OATP-C, MRP2, and UGT1A1, was performed. Serum total and direct (conjugated) bilirubin levels were used as phenotypic indexes. Pharmacokinetic variables of pravastatin, a typical substrate for OATP-C, were obtained from our previous study. Among 23 volunteers, two variants (Va14171le and Ser789Phe) were observed in the MRP2 gene. While there was no apparent effect of these two variants and the UGT1A1*28 on direct bilirubin levels, the OATP-C variants were associated with differences in unconjugated bifirubin levels. Subjects with the OATP-C*15 allele had higher bilirubin levels; unconjugated bilirubin levels in *1b/*1b (n = 3), *1b/*15 (n= 7), and *15/*15 (n = 1) subjects were 0.40 +/- 0.10, 0.77 +/- 0.35, and 0.70 (mg/dL), respectively. In addition, the correlation between unconjugated bifirubin levels and pharmacokinetic parameters of pravastatin revealed that the subjects with higher bilirubin levels had lower non-renal clearance values, and then higher serum concentrations of pravastatin. Large clinical studies are needed to confirm a role of OATP-C in the carrier-mediated uptake of bilirubin in the human liver. (C) 2004 Elsevier B.V. All rights reserved.
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