SEARCHing For A Genetic Cause of Statin Myopathy

The incidence of myopathy secondary to statin use is approximately 1 in 10,000 patients/year on standard doses, but increases with higher doses or concurrent prescription of drugs such as cyclosporine that can inhibit statin metabolism.  Identification of genetic factors that influence an individual’s susceptibility to these complications would improve patient management by identifying those who should take a modified dose or perhaps even avoid a certain agent.

The SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine) Collaborative Group identified a genetic risk factor for myopathy in patients taking simvastatin by screening for 300,000 genetic markers in 12,000 trial patients; looking specifically at those patients taking 80mg simvastatin/day, they compared the prevalence of each genetic marker in those with and without side-effects.  The authors identified a strong association between myopathy and two closely linked variants in the SLCO1B1 gene.  This encodes an organic anion transporting polypeptide which has been demonstrated to regulate the hepatic uptake of statins. Genetic variants in SLCO1B1 may therefore affect the outcomes of patients treated with statins.

Polymorphisms in some solute transporter genes have been previously associated with altered hepatic uptake of pravastatin. Approximately 60% of cases of simvastatin induced myopathy were attributed to SLCO1B1 in this study, and this information could in the future prove useful when treating patients who require high doses of statin and are therefore are at a greater risk of myopathy.

  • The SEARCH Collaborative Group. SLCO1B1 Variants and Statin-Induced Myopathy – A Genomewide Study. N Engl J Med 2008;359:789-99.
  • Nakamara Y (ed) Pharmacogenomics and Drug Toxicity. N Engl J Med 2008;359:856-8.