SLCO1B1 521T > C polymorphism associated with rosuvastatin-induced myotoxicity in Chinese coronary artery disease patients: a nested case–control study

• Published in: European journal of clinical pharmacology Vol. 73; no. 11; pp. 1409 - 1416
• Main Authors: Liu, Ju-E, Liu, Xiao-Ying, Chen, Sheng, Zhang, Yan, Cai, Li-Yun, Yang, Min, Lai, Wei-Hua, Ren, Bin, Zhong, Shi-Long
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2017; Springer Nature B.V
• Subjects: Aged; Alleles; Apolipoprotein E; Apolipoproteins E - genetics; Asian Continental Ancestry Group - genetics; Atorvastatin; Biomedical and Life Sciences; Biomedicine; Cardiovascular disease; Case-Control Studies; Coronary artery; Coronary Artery Disease - drug therapy; Coronary Artery Disease - genetics; Coronary vessels; Cytochrome P-450 CYP3A - genetics; Female; Genetic diversity; Genotype; Health risk assessment; Heart diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Middle Aged; Muscular Diseases - chemically induced; Muscular Diseases - genetics; Pharmacogenetics; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Rosuvastatin Calcium - adverse effects; Rosuvastatin Calcium - therapeutic use; Simvastatin; Single-nucleotide polymorphism; Solute Carrier Organic Anion Transporter Family Member 1b1 - genetics; Statins; SLCO1B1; Genetic variant; Statin-induced myotoxicity
• ISSN: 0031-6970; 1432-1041; 1432-1041
• DOI: 10.1007/s00228-017-2318-z

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.