Genetic determinants of statin-associated myopathy

Lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins), are widely used in the treatment of patients with increased risk of cardiovascular disease, with well-documented benefits. However, in rare cases, lipid-lowering drugs may cause myopathy or rhabdomyolysis, the risk of which is increased by certain drug-drug interactions. Polymorphisms of metabolizing pathways, including CYP, and efflux transporters, such as MDR1 and SLCO1B1, may cause intersubject variability in plasma statin levels and therefore may be responsible for susceptibility to myopathy. The aim of this review is to summarize selected genetic polymorphisms that predispose to statin-related myopathy (including combined studies of myopathy and myalgia). Genome-wide studies suggest that there is a strong candidate variant within the SLCO1B1 gene (rs4149056) for statin-associated myopathy in a UK (European) population. An enhanced understanding of statin-related myopathy may lead to safer drug development and use.