Scientists identify gene responsible for statin-induced m...( BOSTON Statins the popular class of...),Health

BOSTON Statins, the popular class of drugs used to lower cholesterol, are among the most commonly prescribed medications in developed countries. But for some patients, accompanying side effects of muscle weakness and pain become chronic problems and, in rare cases, can escalate to debilitating and even life-threatening damage.

Now a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), helps explain the source of these problems. Published in the December 2007 issue of The Journal of Clinical Investigation, the findings offer the first evidence that a gene known as atrogin-1 plays a key role in statin-related muscle toxicity.

Although it is not known exactly how many of the 500 million individuals who take statins experience muscle pain and weakness, muscle symptoms are generally considered the most common side effects of these medications, explains co-senior author Vikas P. Sukhatme, MD, PhD, Vice Chair of Medicine for Interdepartmental and Translational Programs, Chief of the Division of Nephrology, and Chief of the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.

Statin users describe a wide spectrum of symptoms at the most extreme end is a severe breakdown of skeletal muscle known as rhabdomyolysis, says Sukhatme, who is also the Victor J. Aresty Professor of Medicine at Harvard Medical School (HMS). At the other end is grumbling muscles, milder, more diffuse muscle soreness and cramps. This kind of symptomatic muscle weakness and pain is quite frequent, but often difficult to quantitate.

Known by such trade names as Lipitor, Zocor, Pavacol and Mevacor, statins lower cholesterol by inhibiting HMG-CoA reductase, a key enzyme in cholesterol synthesis.

Approximately five years ago, the studys co-senior author Stewart Lecker, MD, PhD, and colleagues in the HMS laboratory of Alfred Goldberg, MD, first discovered the atrogin-1 gene, so named for its role in muscle atrophy.