Effects of statin treatments and polymorphisms in UGT1A1 and SLCO1B1 on serum bilirubin levels in Chinese patients with hypercholesterolaemia

Autor: Miao Hu, Brian Tomlinson
Rok vydání: 2012
Předmět:
Male
Simvastatin
Organic Anion Transporters
Pharmacology
chemistry.chemical_compound
Risk Factors
Glucuronosyltransferase
Rosuvastatin Calcium
Sulfonamides
biology
Liver-Specific Organic Anion Transporter 1
Middle Aged
Up-Regulation
Organic anion-transporting polypeptide
Phenotype
Treatment Outcome
Female
Animal studies
Cardiology and Cardiovascular Medicine
medicine.drug
Adult
China
medicine.medical_specialty
Statin
medicine.drug_class
Bilirubin
Hypercholesterolemia
Risk Assessment
digestive system
Medication Adherence
Asian People
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
Rosuvastatin
Aged
Analysis of Variance
Polymorphism
Genetic
business.industry
nutritional and metabolic diseases
Fluorobenzenes
Pyrimidines
Endocrinology
chemistry
biology.protein
Hydroxymethylglutaryl-CoA Reductase Inhibitors
SLCO1B1
business
Biomarkers
Zdroj: Atherosclerosis. 223:427-432
ISSN: 0021-9150
Popis: 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 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 .
Databáze: OpenAIRE
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