Genetic and Clinical Factors Are Associated With Statin-Related Myotoxicity of Moderate Severity: A Case-Control Study.

ABSTRACT

We evaluated the contribution of patient-specific clinical and genetic factors to statin-related muscle toxicity (SRM) without a significant creatine kinase elevation (125 cases related to simvastatin or atorvastatin and 481 controls). The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes and clinical factors with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM in univariate analysis (with any statin, odd ratio (OR) = 1.73, 95% confidence interval (CI) = 1.14-2.62, P = 0.010) and this association was influenced by sex (P = 0.006) and BMI (P = 0.02). In multivariate and binary logistic regression analyses, SLCO1B1 rs4149056 genotype (OR = 1.66, 95% CI 1.08-2.54, P = 0.014) and sex (OR = 1.72, 95% CI = 1.15-2.59, P = 0.006) were independently associated with muscle toxicity related to statin treatment. Patient-specific genetic and clinical factors associated with increased systemic exposure to statins are implicated in the full spectrum of SRM, including myalgia in addition to severe myopathy.