DNA Test Identifies Patients Risk of Statin Myopathy

A barrier to statin therapy, a class of drugs used to lower cholesterol, is myopathy associated with elevated systemic drug exposure, which results in muscle pain and weakness, and is a common side effect affecting up to 10% of statin users.

Scientists at the Lawson Health Research Institute (London, ON, Canada) in association with the University of Western Ontario (London, ON, Canada) prospectively recruited 299 patients taking atorvastatin or rosuvastatin. The contribution of clinical variables and transporter gene polymorphisms to statin concentration was assessed using multiple linear regression.

The investigators observed 45-fold variation in statin concentration among patients taking the same dose. After adjustment for gender, age, body mass index, ethnicity, dose, and time from last dose, variants of the solute carrier organic anion transporter family, member 1B1 gene (SLCO1B1 c.521T>C) and the ATP-binding cassette, subfamily G gene (ABCG2 c.421C>A) were important to rosuvastatin concentration. Atorvastatin concentration was associated with SLCO1B1 c.388A>G and c.521T>C, and 4β-hydroxycholesterol, an activity marker, for the cytochrome P450, family 3, subfamily A gene (CYP3A).

In another cohort of 579 patients, genotypes associated with statin concentration were not differently distributed among dosing groups, implying providers had not yet optimized each patient's risk-benefit ratio. Nearly 50% of patients in routine practice taking the highest doses were predicted to have statin concentrations greater than the 90th percentile. As part of their personalized medicine program, the team plans to utilize these pharmacogenetic tests and the algorithm they have created and apply them in a hospital and region wide fashion.

Richard B. Kim, MD, the senior author of the study, said, “We found that commonly occurring genetic variations in the genes that help to clear the drugs from the body, widely referred to as drug transporters, are key predictors of patients who will likely have high statin blood levels. We think those patients with high levels of statins in their blood are at a much greater risk for statin-associated muscle injury." The study was published on July 22, 2013, in the journal Circulation: Cardiovascular Genetics.

Related Links:
Lawson Health Research Institute
University of Western Ontario