Miao Hu1, Brian Tomlinson. 1. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Abstract
OBJECTIVES: In vitro and animal studies showed that statins could increase bilirubin levels by activation of haem oxygenase-1, whereas the effect of statins on serum bilirubin levels in humans remains controversial. The organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) play an important role in the disposition of bilirubin. This study investigated 1) whether common polymorphisms in UGT1A1 and SLCO1B1 influence bilirubin levels; 2) whether statin treatments affect bilirubin levels; and 3) whether the polymorphisms examined influence the drug effect. METHODS: Associations between common polymorphisms in UGT1A1 and SLCO1B1 and the serum bilirubin levels on no lipid-lowering treatment were analyzed in 379 Chinese patients with hypercholesterolaemia. Effects of simvastatin 40 mg daily and rosuvastatin 10 mg daily on the bilirubin levels were compared in 236 subjects with good compliance to both statins. RESULTS: The UGT1A1 polymorphisms associated with reduced enzyme activity were significantly associated with increased baseline bilirubin levels. The bilirubin levels were increased from a geometric mean (95% CI) of 10.9 (10.3-11.4) μmol/L at baseline to 11.6 (11.1-12.0) μmol/L with rosuvastatin and 12.5 (11.9-13.0) μmol/L with simvastatin and the increase was greater with simvastatin (P < 0.001). There was no relationship between polymorphisms in UGT1A1 or SLCO1B1 and changes in bilirubin levels with the two statins. CONCLUSIONS: This study showed that the polymorphisms in UGT1A1, but not SLCO1B1, were associated with serum bilirubin levels in Chinese patients. Statins increased bilirubin levels and this effect was independent of the polymorphisms in UGT1A1 and SLCO1B1.
OBJECTIVES: In vitro and animal studies showed that statins could increase bilirubin levels by activation of haem oxygenase-1, whereas the effect of statins on serum bilirubin levels in humans remains controversial. The organic anion transporting polypeptide 1B1 (OATP1B1, gene SLCO1B1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) play an important role in the disposition of bilirubin. This study investigated 1) whether common polymorphisms in UGT1A1 and SLCO1B1 influence bilirubin levels; 2) whether statin treatments affect bilirubin levels; and 3) whether the polymorphisms examined influence the drug effect. METHODS: Associations between common polymorphisms in UGT1A1 and SLCO1B1 and the serum bilirubin levels on no lipid-lowering treatment were analyzed in 379 Chinese patients with hypercholesterolaemia. Effects of simvastatin 40 mg daily and rosuvastatin 10 mg daily on the bilirubin levels were compared in 236 subjects with good compliance to both statins. RESULTS: The UGT1A1 polymorphisms associated with reduced enzyme activity were significantly associated with increased baseline bilirubin levels. The bilirubin levels were increased from a geometric mean (95% CI) of 10.9 (10.3-11.4) μmol/L at baseline to 11.6 (11.1-12.0) μmol/L with rosuvastatin and 12.5 (11.9-13.0) μmol/L with simvastatin and the increase was greater with simvastatin (P < 0.001). There was no relationship between polymorphisms in UGT1A1 or SLCO1B1 and changes in bilirubin levels with the two statins. CONCLUSIONS: This study showed that the polymorphisms in UGT1A1, but not SLCO1B1, were associated with serum bilirubin levels in Chinese patients. Statins increased bilirubin levels and this effect was independent of the polymorphisms in UGT1A1 and SLCO1B1.
Authors: Kimberly S Collins; Ingrid F Metzger; Brandon T Gufford; Jessica B Lu; Elizabeth B Medeiros; Victoria M Pratt; Todd C Skaar; Zeruesenay Desta Journal: Drug Metab Dispos Date: 2019-12-30 Impact factor: 3.922
Authors: Kwok-Leung Ong; Matthew A Allison; Bernard M Y Cheung; Ben J Wu; Philip J Barter; Kerry-Anne Rye Journal: PLoS One Date: 2014-04-11 Impact factor: 3.240