Gene Linked to Muscle Weakness Triggered by ZocorJul 24, 2008 | Parker Waichman LLP
British researchers have just announced yesterday that they have located a gene responsible for muscle pain or weakness that is experienced by some people who are taking the statin drug Zocor. Statins fight "bad" cholesterol. This new finding could lead to routine testing to identify those patients who should receive either a different class of drug or should be kept on a lower dose.
The research group was led by Rory Collins of the University of Oxford and the team used a new technology to rapidly scan about 300,000 points on the human genetic code hoping to locate a reason for why 85 in the group developed muscle weakness as compared a similar group of 90 who did not. The difference was found on a gene involved in the way the liver regulates statin levels.
Those with two normal genes had only a 0.6 percent risk of developing muscle weakness, known as myopathy, during the first year of taking 80 milligrams daily of the Merck drug Zocor, known generically as simvastatin. If a patient had one normal and one abnormal gene—this occurred in about 30 percent of the group studied—the risk increased to three percent. Those with two abnormal genes—this occurred in two percent of the population—saw an increase in developing muscle weakness by 18 percent. The researchers report that the abnormal gene appears to be responsible for 60 percent of all myopathy cases,. "It's a very easy, inexpensive test to do," Collins said. "You're talking less than a dollar once you've got the DNA extracted."
The screening is expected to be very helpful when doctors feel the need to aggressively lower bad cholesterol levels, he said. "Identifying people who don't have this variant will allow the doctor and patient to be assured that they are much less likely to get myopathy with the high dose or with statins combined with other drugs. I think it can be used to get greater efficacy for particular patients while improving safety," Collins said.
The discovery is less likely to affect those patients taking 20 to 40 milligrams of Zocor daily, or those patients taking standard doses of other statins, since the incidence of myopathy for that population is only about one per 10,000 patients per year. The research is published in the New England Journal of Medicine.
In a Journal editorial that accompanied the study, Yusuke Nakamura of the University of Tokyo said the amount of muscle damage seen in the new study was mild and reversible. Regardless, statins can also cause rhabdomyolysis, which is a much more serious form of muscle damage. Rhabdomyolysis can affect the kidney and, in rare instances, can even lead to death. Nakamura said further tests are needed to see if a variant of the same gene is also responsible for that condition.
Collins said he believes that it is and that rhabdomyolysis is, “part of the same problem. This is essentially a gene for rhabdomyolysis and myopathy," Collins added.