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Common Variant Implicated in Statin-Related Muscle Aches

NEW YORK (GenomeWeb) – New research suggests a relatively common genetic variant can contribute to statin side effects — namely the muscle pain, or myalgia, that occurs in a subset of individuals who are prescribed the cholesterol lowering drugs.

Members of an international team led by investigators at the University of Dundee analyzed electronic medical records for nearly 12,000 individuals from GoDARTS, a Scottish study focused on genetic and pharmacogenetic contributors to diabetes and other conditions. In that cohort — and in validation groups encompassing thousands more individuals from around the world — they saw ties between an immune gene called LILRB5 and statin non-adherence or intolerance.

For individuals carrying two copies of an LILRB5 variant known as Asp247, the team explained, cases of muscle pain or myalgia marked by elevated levels of a creatine phosphatase enzyme marker of muscle damage were more common. But this group also appeared more prone to statin intolerance at relatively low doses, according to results reported online yesterday in the European Heart Journal.

"Adverse reactions are the driving reason for therapy cessation, which puts the patient at an increased risk of a cardiovascular event," corresponding author Colin Palmer, a pharmacogenetics and pharmacogenomics researcher at the University of Dundee, said in a statement. "This is the first time a genetic variant thought to be involved in the repair and regeneration of muscles has been found to be associated with this side effect."

The same variant was previously linked to altered creatine phosphokinase enzyme levels, the authors noted, prompting speculation that it might contribute not only to general muscle aches but also statin-related muscle pain.

For the first stage of the study, the researchers brought together data for 11,912 statin-prescribed GoDARTS participants, focusing on LILRB5 genotypes already associated with creatine phosphokinase and serum lactate dehydrogenase markers of muscle damage.

In the GoDARTs individuals, the team found that homozygous Asp247 carriers were almost twice as likely to experience general statin intolerance, on average, while intolerance to low statin doses was roughly 1.4 times as common in this group.

The researchers tapped into data from three replication cohorts comprised of hundreds of individuals with statin-induced myopathy and thousands without to explore the apparent association in more detail. In all but one of the individual cohorts — and in a meta-analysis spanning all of the available cases and controls — they again saw an uptick in muscle aches amongst individuals carrying two copies of the Asp247 variant.

Although more work is needed to unravel the mechanism of muscle aches in the Asp247 carriers, the findings support the notion that immune function and genetic predisposition can contribute to statin-induced myalgia and other forms of muscle pain. And because the alternative version of this variant might protect against muscle pain, the researchers suspect that it might prove useful in untangling other contributors to statin-specific muscle pain.

"The LILRB5 Asp247Gly genotype presents a unique opportunity to probe the immune mechanisms behind the phenomena of muscle pain specific to statins compared to 'constitutive' muscle pain that appears in LILRB5 Asp247 homozygotes," Palmer and his co-authors wrote.