The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment.

摘要: Objective Our objective was to investigate the interactions between common polymorphisms in ABCB1, CYP3A4, and CYP3A5 genes lipid-lowering efficacy safety of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor simvastatin. Methods One hundred sixteen hypercholesterolemic patients were prospectively screened by physical examination, medical history, clinical laboratory evaluation included this study. Subjects entering study treated with 20 mg/d simvastatin. Plasma lipid lipoprotein levels measured before treatment, after 2 months 6 treatment. Ninety-nine completed 6-month follow-up association analysis for treatment efficacy. Seventeen subjects who had adverse drug reactions (ADRs) simvastatin (ADR group) could not complete analyses safety. Myalgia observed 15 17 only ADR analyses, but other ADRs also observed. defined as proximal or diffuse muscle pain, tenderness, weakness, both pain normal slightly increased serum creatine phosphokinase levels. ABCB1 (1236C>T, 2677G>A/T, 3435C>T), CYP3A4 (−392A>G), (6986A>G) allele variants determined polymerase chain reaction restriction mapping. Results After adjustment covariates, carriers 1236T variant a greater reduction total cholesterol low-density compared homozygotes wild-type (−29.0% [95% confidence interval (CI), −25.9 −32.5] versus −24.2% CI, −19.0 −29.3] [P = .042] −39.6% −35.8 −44.0] −33.8% −27.4 −40.2] .042], respectively). Similar results 2677G>A/T polymorphism haplotype data. The 1236T, 2677non-G, 3435T alleles less frequent cases than non-ADR group (P G CYP3A5*3 tolerability simvastatin. Conclusions Our data suggest an gene simvastatin. Clinical Pharmacology & Therapeutics (2005) 78, 551–558; doi: 10.1016/j.clpt.2005.08.003