Article

Individualized risk for statin-induced myopathy: Current knowledge, emerging challenges and potential solutions

Department of Medicine, Vanderbilt University Medical Center, Oates Institute for Experimental Therapeutics, Nashville, TN, USA.
Pharmacogenomics (Impact Factor: 3.22). 04/2012; 13(5):579-94. DOI: 10.2217/pgs.12.11
Source: PubMed

ABSTRACT

Skeletal muscle toxicity is the primary adverse effect of statins. In this review, we summarize current knowledge regarding the genetic and nongenetic determinants of risk for statin induced myopathy. Many genetic factors were initially identified through candidate gene association studies limited to pharmacokinetic (PK) targets. Through genome-wide association studies, it has become clear that SLCO1B1 is among the strongest PK predictors of myopathy risk. Genome-wide association studies have also expanded our understanding of pharmacodynamic candidate genes, including RYR2. It is anticipated that deep resequencing efforts will define new loci with rare variants that also contribute, and sophisticated computational approaches will be needed to characterize gene-gene and gene-environment interactions. Beyond environment, race is a critical covariate, and its influence is only partly explained by geographic differences in the frequency of known pharmacodynamic and PK variants. As such, admixture analyses will be essential for a full understanding of statin-induced myopathy.

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Available from: Tesfaye M Baye, Feb 06, 2015
    • "A range of risk factors have been reported for statin-associated myopathy, including female gender (though not in all studies), low body mass index, older age, intense physical exercise, comorbidities such as hypothyroidism, and – most importantly – interactions with other drugs such as amiodarone and fibrates.5 In candidate gene studies, polymorphisms in a variety of genes affecting statin pharmacokinetics or pharmacodynamics have also been reported to influence statin-induced myopathy (reviewed in 32). "
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