Association of SLCO1B1 and ABCB1 Genetic Variants with Atorvastatin-induced Myopathy in Patients with Acute Ischemic Stroke

Abstract

Background:Certain patients experience muscle-related adverse effects after taking atorvastatin. Genetic factors play an important role in the occurrence of statin-induced myopathy.Aim:We aimed to identify genetic variants associated with statin-induced myotoxicity.Methods:We prospectively enrolled 1,102 acute ischemic stroke patients who underwent atorvastatin treatment for the first time after admission. Patients were separated into case and control groups after a follow-up of 3 months. We used a biochemical definition of myopathy consisting of serum creatine kinase values more than ten times the upper limit of normal for the reference laboratory (150 U/L). Fifty single nucleotide polymorphisms (SNPs) from seven genes of ABCB1, CoQ2, HTR3B, RYR2, CYP3A5, HTR7 and SLCO1B1 were selected and genotyped. The effects of genetic polymorphisms on myopathy were observed.Results:61 cases and 110 controls were recruited in the study. Compared with the controls, the cases had a significant higher mutant frequency of the allele A (ABCB1, rs2373588) (OR = 2.01, 95%CI = 1.10-3.67, P = 0.001) and a significant lower mutant frequency of the allele A (SLCO1B1, rs976754) (OR = 1.85, 95%CI = 1.12-3.03, P = 0.042). Genotypes or alleles of the other SNPs had no significant difference between the two groups (P > 0.05).Conclusion:Our findings reveal that SLCO1B1 and ABCB1 genetic variants are associated with statin-induced myopathy. These are valuable biomarkers for the evaluation of atorvastatin safety.