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Muscle Pain and Statins

A Gene May Provide Clue About Muscle Pain Caused By Statin Drugs

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Updated January 02, 2008

Statins are a group of popular and effective cholesterol-lowering medications that work by blocking a key protein, HMG-CoA reductase, which is responsible for making cholesterol in the liver. Statins target all aspects of your lipid profile, lowering LDL cholesterol and triglycerides while raising HDL cholesterol. Unfortunately, there are rare but troublesome side effects of statins, ranging from mild muscle weakness to life-threatening rhabdomyolysis. Scientists have recently reported that they may have found the gene responsible for this -- atrogin-1.

Previous studies have shown that the gene atrogin-1 is turned on at the beginning stages of the breakdown of muscle (muscle wasting). This is associated with illnesses such as cancer, sepsis, and AIDS. When the atrogin-1 gene is not active, muscle wasting does not occur.

Scientists at Beth Israel Deaconess Medical Center in Boston, Massachusetts felt that atrogin-1 might also play a role in the development of myopathies in those taking statins. To test this, the investigators gave a statin, Mevacor (lovastatin), to cultured muscle cells, zebra fish, and humans. They found that humans taking Mevacor had higher levels of atrogin-1 than those not taking the drug. The more Mevacor given to the cells and zebra fish, the more likely it was that muscle damage would occur. When atrogin-1 was removed from the cells, the drug did not cause muscle damage.

This information is preliminary, but it provides us an understanding of what may be causing muscle pain in statin users, and why some individuals taking statins may be more susceptible to this than others. In the future, this may allow your health care provider to identify if you are at risk for statin-related myopathies, ranging from mild muscle pain to life-threatening rhabdomyolysis. Additionally, scientists may be able to manipulate this gene, or others involved, to prevent muscle damage caused by statins.

Sources:

Hanai JI, Cao P, Tanksale P, et al. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 117(12):3940-3951.

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