Muscle pain in people on statins may have a genetic link

A new genetics study adds fuel to the debate about muscle aches that have been reported by many people taking popular cholesterol-lowering drugs called statins.

About 60 percent of people of European descent carry a genetic variant that may make them more susceptible to muscle aches in general. But counterintuitively, these people had a lower risk of muscle pain when they took statins compared with placebos, researchers report August 29 in the European Heart Journal.
Millions of people take statins to lower cholesterol and fend off the hardening of arteries. But up to 78 percent of patients stop taking the medicine. One common reason for ceasing the drugs’ use is side effects, especially muscle pain, says John Guyton, a clinical lipidologist at Duke University School of Medicine.

It has been unclear, however, whether statins are to blame for the pain. In one study, 43 percent of patients who had muscle aches while taking at least one type of statin were also pained by other types of statin (SN: 5/13/17, p. 22). But 37 percent of muscle-ache sufferers in that study had pain not related to statin use. Other clinical trials have found no difference in muscle aches between people taking statins and those not taking the drugs.

The new study hints that genetic factors, especially ones involved in the immune system’s maintenance and repair of muscles, may affect people’s reactions to statins. “This is a major advance in our understanding about myalgia,” or muscle pain, says Guyton, who was not involved in the study.

People with two copies of the common form of the gene LILRB5 tend to have higher-than-usual blood levels of two proteins released by injured muscles, creatine phosphokinase and lactate dehydrogenase. Higher levels of those proteins may predispose people to more aches and pains. In an examination of data from several studies involving white Europeans, people with dual copies of the common variant were nearly twice as likely to have achy muscles while taking statins as people with a less common variant, Moneeza Siddiqui of the University of Dundee School of Medicine in Scotland and colleagues discovered.

But when researchers examined who had pain when taking statins versus placebos, those with two copies of the common variant seemed to be protected from getting statin-associated muscle pain. Why is not clear.
People with double copies of the common form of the gene who experience muscle pain may stop taking statins because they erroneously think the drugs are causing the pain, study coauthor Colin Palmer of the University of Dundee said in a news release.

The less common version of the gene is linked to reduced levels of the muscle-damage proteins, and should protect against myalgia. Yet people with this version of the gene were the ones more likely to develop muscle pain specifically linked to taking statins during the trials.

The finding suggests that when people with the less common variant develop muscle pain while taking statins, the effect really is from the drugs, the researchers say.

But researchers still don’t know the nitty-gritty details of how the genetic variants promote or protect against myalgia while on statins. Neither version of the gene guarantees that a patient will develop side effects — or that they won’t. The team proposes further clinical trials to unravel interactions between the gene and the drugs.

More study is needed before doctors can add the gene to the list of tests patients get, Guyton says. “I don’t think we’re ready to put this genetic screen into clinical practice at all,” he says. For now, “it’s much easier just to give the patient the statin” and see what happens.