GAUSS-3: Pathogenesis of Statin-Associated Muscle Symptoms

There may be significant genome-wide associations in patients with statin-associated muscle symptoms, according to the results of a genome-wide association study of the GAUSS-3 Trial presented Nov. 15 during AHA 2016.

Erik Stroes, MD, et al., conducted a robust, discovery-based study in subjects enrolled in GAUSS-3 and other evolocumab trials (RUTHERFORD-1/2 and LAPLACE-1) to identify genes associated with statin-associated muscle symptom. Genotypes from 771 adults were obtained and statin-associated muscle symptoms were established in 149 patients via correct reporting of muscle symptoms during the statin re-challenge period (132 patients) or by documented CK greater than 10 times the upper limit of normal with muscle symptoms while on statins (17 patients).

The results of the trial suggest polygenic inheritance of statin-associated muscle symptoms. Several genome-wide significant associations were discovered, i.e., common single-nucleotide polymorphisms (SNPs) located in chr2q21, chr17q24 and chr21q22. Using an additive effect model, carriers of a risk allele for genome-wide significant SNPs in chr2q21 and chr17q24 loci had an increased risk of statin-associated muscle symptoms.

The authors note that "these novel SNPs, not previously described in the statin intolerance literature, may provide insight into the pathogenesis of statin-associated muscle symptoms and help identify definitive biomarkers."

Keywords: AHA16, American Heart Association, AHA Annual Scientific Sessions, Cross-Over Studies, Double-Blind Method, Genome-Wide Association Study, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Muscles

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