Ju-E Liu1,2,3, Xiao-Ying Liu1,2, Sheng Chen4, Yan Zhang5, Li-Yun Cai1,2, Min Yang3, Wei-Hua Lai3, Bin Ren6, Shi-Long Zhong7,8. 1. Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangzhou, 510080, China. 2. Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg.1112, Guangzhou, 510080, People's Republic of China. 3. Department of Pharmacy of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. 4. Department of General Surgery of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. 5. Guangzhou Higher Education Mega Center Health Industrial Science and Technology Park Investment Management Co. Ltd. Guangzhou Gene Denovo Biotechnology Co. Ltd, Guangzhou, China. 6. Department of Pharmacy, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China. 7. Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangzhou, 510080, China. zhongsl@hotmail.com. 8. Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg.1112, Guangzhou, 510080, People's Republic of China. zhongsl@hotmail.com.
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.
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.
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