Gene Behind Serious Statin Risk
Muscle Condition From Cholesterol Drugs Linked to Gene Variant
Aug. 20, 2008 -- A variant gene causes more than 60% of cases of a serious side effect of cholesterol-lowering statin drugs -- muscle pain and weakness.
Statin drugs -- Lipitor, Pravachol, Crestor, Lescol, Mevacor, and Zocor -- are considered remarkably safe. But one in every 10,000 patients per year develops drug-related muscle trouble. Very rarely, this myopathy leads to muscle breakdown and fatal kidney failure.
Oxford University researcher Rory Collins, MB, and the SEARCH Collaborative Group performed genome-wide scans of heart attack survivors taking high doses (80 mg/day) of Zocor in a large-scale clinical trial. They compared the 98 patients who developed myopathy with 98 patients who did not.
"We provide compelling evidence that at least one common variant in the SLCO1B1 gene substantially alters the risk of [Zocor]-induced myopathy," Collins and colleagues conclude. "These findings are likely to apply to other statins because myopathy is a class effect, and SLCO1B1 polymorphisms affect the blood levels of several statins."
The gene variant is relatively common. It alters the function of a gene that regulates drug uptake in the liver. People who inherit two copies of the gene had a 17-fold increased risk of muscle problems when taking high doses of Zocor. Those with just a single copy had a 4.5-fold increased risk.
Collins and colleagues suggest that before starting high-dose statin treatment, patients may benefit from genetic testing to see whether they are at risk of side effects.
Yusuke Nakamura, MD, PhD, director of the Human Genome Center at the University of Tokyo, agrees.
In an editorial accompanying the Collins team's report in the Aug. 21 issue of the New England Journal of Medicine, Nakamura suggests that avoiding high doses of statins in people who carry the gene could reduce statin-related muscle problems by 60%.