Genetic Determinants of Statin-Associated Myopathy

Abstract

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.

Keywords: :

• genetic polymorphisms
• rhabdomyolysis
• SNP
• statin-induced myopathy

Acknowledgements

We are grateful to Kari Kivistö and Rob Hughes for earlier comments regarding this review.

Financial & competing interests disclosure

MM has received grants from Pfizer and from the Serious Adverse Events Consortium (collaboration of industry and academia). MM is supported by a post-doctoral fellowship from the NCCRCD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

MM has received grants from Pfizer and from the Serious Adverse Events Consortium (collaboration of industry and academia). MM is supported by a post-doctoral fellowship from the NCCRCD. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.