SLCO1B1 521T > C polymorphism associated with rosuvastatin-induced myotoxicity in Chinese coronary artery disease patients: a nested case–control study
- 15 August 2017
- journal article
- pharmacogenetics
- Published by Springer Science and Business Media LLC in European Journal of Clinical Pharmacology
- Vol. 73 (11), 1409-1416
- https://doi.org/10.1007/s00228-017-2318-z
Abstract
Purpose This nested case–control study aimed to evaluate the association of candidate genetic variants with statin-induced myotoxicity in Chinese patients with coronary artery disease (CAD). Methods One hundred forty-eight Chinese patients experiencing statin-induced myotoxicity were included in our study, and 255 patients without muscular side effects served as controls. Five SNPs in CYP3A5, SLCO1B1, and APOE were genotyped. The effect of genetic variants on statin-induced myotoxicity was assessed. Results Patients who carried at least one SLCO1B1 521C allele had a higher risk for myotoxicity (OR = 1.69, 95%CI = 1.07–2.67, P = 0.024). Significant association was found between SLCO1B1 521C mutant allele mutation and risk of myotoxicity in individuals that received rosuvastatin (OR = 3.67, 95%CI = 1.42–9.47, P = 0.007). However, non-significant association was observed between 521C mutant allele and risk of myotoxicity (P > 0.5) in patients that received atorvastatin and simvastatin. The other four single nucleotide polymorphisms (SNPs), namely rs776746, rs2306283, rs7412, and rs429358, showed no significant association with any statin induced myotoxicity (P > 0.5). Conclusions SLCO1B1 (rs4149056, 521T > C) is associated with statin-induced myotoxicity in Chinese patients with coronary artery disease. In addition, SLCO1B1 521C mutant allele increased the risk of rosuvastatin-associated myotoxicity.Keywords
Funding Information
- National Nature Science Foundation of China (81373486, 81673514)
- National key research and development program (2016YFC0905000, 2017YFC0909301)
- Science and Technology Development Projects of Guangdong Province, China (2016B090918114, 2013B021800157)
- Science and Technology Development Projects of Guangzhou, Guangdong (201510010236, 201604020096)
This publication has 31 references indexed in Scilit:
- Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phaseThe Lancet, 2017
- Impact of ABCG2 and SLCO1B1 polymorphisms on pharmacokinetics of rosuvastatin, atorvastatin and simvastatin acid in Caucasian and Asian subjects: a class effect?European Journal of Clinical Pharmacology, 2015
- Genetics is a major determinant of expression of the human hepatic uptake transporter OATP1B1, but not of OATP1B3 and OATP2B1Genome Medicine, 2013
- Is there clinical benefit to routine enzyme testing of patients on statins?Expert Opinion on Drug Safety, 2011
- Genetic involvement in statins induced myopathy. Preliminary data from an observational case–control studyAtherosclerosis, 2010
- The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side EffectsJournal of Invasive Cardiology, 2009
- Different Effects of SLCO1B1 Polymorphism on the Pharmacokinetics of Atorvastatin and RosuvastatinClinical Pharmacology & Therapeutics, 2007
- SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acidPharmacogenetics and Genomics, 2006
- SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatinClinical Pharmacology & Therapeutics, 2006
- Incidence of Hospitalized Rhabdomyolysis in Patients Treated With Lipid-Lowering DrugsJAMA, 2004