Scientists may have found a way to test for and possibly avoid the most serious side effect of cholesterol-lowering statin drugs, one of the top-selling medicines in the world.

In rare cases, statins can cause muscle pain and weakness. Researchers have identified a genetic variation that seems to predict more than half of these cases. People on statins who have the variant were about five to 17 times more likely to develop muscle problems, a serious side effect that can lead to muscle breakdown, kidney failure, and death.

The finding raises hope that a test could be developed to screen heart patients to find out who is at greatest risk. Normally, muscle weakness caused by statins affects 1 out of 10,000 patients a year.

“It could become a very simple check,” said Rory Collins of the University of Oxford, who co-authored the study published in today’s New England Journal of Medicine.

But doctors say having this knowledge doesn’t mean the millions taking statins should be tested, especially those who are having no problem.

“I would recommend extreme caution in testing for this,” a University of Wisconsin-Madison cardiologist who had no role in the research, Dr. James Stein, said. “It could potentially lead to people not taking lifesaving drugs just because there’s an excess risk” of a side effect.

Statins are mostly prescribed to prevent heart attacks in people with clogged arteries and work by dramatically lowering LDL or “bad cholesterol.” Last year, global sales for statins topped $14.8 billion, according to health care research firm IMS Health.

Doctors are increasingly prescribing higher statin doses to drive down bad cholesterol. The risk of muscle problems increases when people take statins at higher doses or with other medications.

The genetic analyses drew from two previous large studies that were in part funded by Merck & Co., which makes the one-time cholesterol blockbuster, Zocor, now available as the low-cost generic simvastatin.

The first involved 85 statin users with muscle weakness and 90 controls taken from a sample of 12,000 people. The participants — all of European descent — took higher than normal doses of simvastatin.

Using DNA samples, researchers found a gene variation in more than 60 percent of those with muscle weakness. The variant makes a protein less effective at carrying statins into the liver where the drug has the greatest effect.

Muscle weakness was mild and reversible if people stopped taking statins. Researchers confirmed the results in a second separate study involving people who took a lower dose. Since the genetic analyses were based on treatment with one type of statin, it’s unclear if the results hold true for other cholesterol drugs.

Dr. Wayne Grody, who heads the DNA Diagnostic Laboratory at the University of California, Los Angeles, said a commercial test costing $200 to $300 could be easily developed if it’s proven in experiments.

But Dr. Grody cautioned it’s too early for widespread use since not all the muscle weakness cases could be linked to the genetic variation.

“It’s not going to be absolutely predictive,” he said.