OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation.

OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Research Abstract Details 

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OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Abstract Text:

Wei Zhang,Yi-Jing He,Zhou Gan,Lan Fan,Qing Li,An Wang,Zhao-Qian Liu,Sheng Deng,Yuan-Fei Huang,Lin-Yong Xu,Hong-Hao Zhou,Wei Zhang,Yi-Jing He,Zhou Gan,Lan Fan,Qing Li,An Wang,Zhao-Qian Liu,Sheng Deng,Yuan-Fei Huang,Lin-Yong Xu,Hong-Hao Zhou,

1. Elevated serum bilirubin levels are caused mainly by liver diseases, haematolysis, genetic defects and drug intake. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). The present study was performed to determine the association between SLCO1B1 gene polymorphisms and serum bilirubin levels in vivo. Moreover, the effects of administration of low-dose rifampicin on serum bilirubin levels in different SLCO1B1 genotypes was examined. 2. Serum bilirubin levels were examined in 42 healthy volunteers who had been analysed for SLCO1B1 genotype (seven, 13, 14 and eight with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively). Among them, 24 subjects (seven, seven, eight and two with SLCO1B1 genotypes *1a/*1a, *1b/*1b, *1b/*15 and *15/*15, respectively) were selected to participate in an open-label, two-phase clinical trial. Each was given 450 mg rifampicin orally once daily at 2000 hours for 5 consecutive days. Serum bilirubin concentrations at 0800 hours on the 1st and 6th days were compared between the different SLCO1B1 genotypes. 3. In the 42 volunteers, the mean (+/-SD) serum UCB in both SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (11.07 +/- 2.31, 13.01 +/- 3.87 and 8.21 +/- 2.68 micromol/L, respectively; P = 0.009 and P < 0.001). Total bilirum (T.BIL) in both the SLCO1B1*1b/*15 and *15/*15 groups was significantly higher than that in the SLCO1B1*1b/*1b group (16.69 +/- 4.09, 20.71 +/- 5.12 and 13.06 +/- 5.12 micromol/L, respectively; P = 0.029 and P < 0.001). The direct bilirubin (D.BIL) in the SLCO1B1*15/*15 group was significantly higher than that in the SLCO1B1*1b/*1b group (7.69 +/- 1.81 vs 4.85 +/- 1.81 micromol/L, respectively; P = 0.001). Rifampicin significantly increased UCB, T.BIL and D.BIL concentrations in 24 healthy volunteers (17.68 +/- 5.96 vs 13.95 +/- 4.44 micromol/L (P = 0.040), 5.72 +/- 2.01 vs 4.35 +/- 1.50 micromol/L (P = 0.028) and 12.00 +/- 4.26 vs 9.61 +/- 3.15 micromol/L (P = 0.035), respectively). However, the extent of the increase in serum bilirubin caused by 450 mg rifampicin for 5 days was not affected by SLCO1B1 genotype. 4. Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the serum bilirubin level. SLCO1B1*15 carriers had higher baseline serum UCB, T.BIL and D.BIL levels compared with subjects with the SLCO1B1*1a/*1a and SLCO1B1*1b/*1b genotypes. SLCO1B1*15/*15 homozygotes are more susceptible to hyperbilirubinaemia. Serum bilirubin levels could be increased by low-dose rifampicin administration, but the extent of the increase was not associated with SLCO1B1 genotype.

OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Publishing Authors By Initials

W Zhang,YJ He,Z Gan,L Fan,Q Li,A Wang,ZQ Liu,S Deng,YF Huang,LY Xu,HH Zhou,W Zhang,YJ He,Z Gan,L Fan,Q Li,A Wang,ZQ Liu,S Deng,YF Huang,LY Xu,HH Zhou,

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OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical and experimental pharmacology & physiolog

VOLUME: 34

Page Numbers: 1240-4

Journal Abbreviation: Clin. Exp. Pharmacol. Physiol.

ISSN: 0305-1870

DAY: 1

MONTH: Dec

YEAR: 2007

OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Information

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LANGUAGE: eng

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Grant and Affiliation Information for OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation.

AFFILIATION: Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.

Country: Australia

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MEDLINETA: Clin Exp Pharmacol Physiol

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