Genetic variant predisposes individuals to statin- and non statin-related muscle pain

A study has identified a common genetic variant of the LILRB5 gene that predisposes people to developing muscle aches regardless of whether they have been taking a statin^[1]
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The researchers said the findings indicate that these individuals could misattribute such symptoms to statins if they start taking the drugs and that, in future, genetic screening could be used to predict people’s response to the drugs.

“It would be possible to test prospective statin users for key genetic variants, including LILRB5, to prevent people being put on statins if they are likely to have an adverse reaction to them,” said study author Colin Palmer from the University of Dundee.

“Adverse reactions are the driving reason for therapy cessation, which puts the patient at an increased risk of a cardiovascular event.”

The study

The team studied medical records on 11,947 statin users from a Scottish study into the genetics of diabetes, including around 98,000 person years of statin exposure.

The researchers split the patients into two statin intolerance phenotypes: those who were non-adherent and showed raised levels of creatine phosphokinase (general statin intolerance) and those who were intolerant to the lowest dose of statin therapy before being switched to two or more other statins (low-dose intolerance).

They found that individuals who carried two copies of the LILRB5 genetic variant, Asp247, had increased odds of both types of intolerance. These individuals were 1.96-fold more likely to have general statin intolerance and 1.43-fold more likely to have low-dose intolerance than those carrying another variant, referred to as 247Gly.

The team replicated these findings in two out of three cohorts from previous studies. In one of these, a randomised trial called JUPITER, they found that those with two copies of the Asp247 variant had a similar risk of developing myalgia whether they were assigned to placebo or the statin, indicating that their increased risk of myalgia was independent of statin therapy. By contrast, those with the 247Gly variant only had an increased risk of myalgia when assigned to the statin.

Future benefits

The researchers say the results mean that people carrying the LILRB5 Asp247 variant could, when treated with statins, wrongly attribute their muscle pain to the drugs. They also suggest that doctors could avoid prescribing statins to people at risk of developing statin-specific muscle pain if pre-treatment genetic screening was available.

Around 30% of people being prescribed statins discontinue them due to muscle discomfort within the first year of therapy. However, many of these people will find a different statin or a lower dose of the same statin tolerable.

Professor Metin Avkiran, associate medical director of the British Heart Foundation, said that the findings are unlikely to have a marked impact on patient treatment as the benefits of statin therapy far outweigh the risks.

“However, they may help the development of new methods for the identification of people who are prone to develop myopathy during statin therapy and therefore are potentially more suitable to receive alternative treatments,” he said.

Akviran added that future research should now work out how the LILRB5 variant affects the function of the gene’s protein product and how that, in turn, might alter muscle integrity and susceptibility to injury, with or without statin treatment.