Jul 24, 2008 - Health + Traits

Gene Variant May Increase Risk for Rare Side Effect of Cholesterol-Lowering Drugs

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By lowering blood levels of “bad cholesterol,” or LDL, statins can lower the risk of heart attack and stroke. But the drugs are not without side effects – about one patient out of 10,000 experiences a form of muscle pain and/or weakness known as myopathy.

The SEARCH Collaborative Group

A report published yesterday in the New England Journal of Medicine suggests that a variation in a gene previously linked to how the body processes statins may be partially to blame.

The SEARCH Collaborative Group, a large consortium of scientists studying the use of high simvastatin (Zocor/Lipex) doses in British patients who have previously had heart attacks, found a genetic variant associated with an increased risk of myopathy.


Out of about 6,000 people taking 80 mg daily of simvastatin (the usual dose is 20-40 mg), researchers identified 85 who either had myopathy or whose bloodwork suggested they were on the verge of developing it.

When these people were compared to 90 people who were on high-dose simvastatin but had no signs of muscle problems, the researchers found that one version of the variant increased a person’s odds of myopathy 4.9 times and two variants increased the odds 16.9 times.

The researchers also found an association between one variant and myopathy in the Heart Protection Study. That study compared 10,200 people taking 40 mg of simvastatin with a similar number of people taking a placebo. In this case, however, the effect of the variant was much smaller, increasing the odds of myopathy by only 2.6 times. Only 23 of the simvastatin-taking patients in this study had myopathy.

More Serious Side Effects

The myopathy experienced by both patients in the New England Journal of Medicine report was mild and reversible. There is, however, a potentially fatal (but even more rare) form of muscle breakdown called rhabdomyolysis that has also been linked to statins. More research will be needed to investigate whether rs4149056 is also associated with rhabdomyolysis.

In addition to simvastatin, five other statins are available in the United States: lovastatin (Mevacor/Altocor), pravastatin (Pravachol/Selektine/Lipostat), fluvastatin (Lescol), atorvastatin, (Lipitor/Torvast), and rosuvastatin (Crestor). The authors of the study say that their findings likely apply to those drugs as well — myopathy is known to be a side-effect of all statins and variants in the gene where rs41419056 is found are known to affect blood levels of several statins.

Sixty percent of the myopathy cases observed in the study of patients taking 80 mg of simvastatin could be attributed to the C version of rs4149056. This suggests that avoiding giving high doses of statins to people who carry this version of the SNP could significantly reduce the incidence of myopathy, wrote Yusuke Nakamura in an editorial accompanying the study. However, he added, “Further investigation is required to identify the optimal therapeutic approach.”

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