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RYR1 and CACNA1S genetic variants identified withf statin-associated muscle symptoms.

Pharmacogenomics 2018 October 17
AIM: To examine the genetic differences between subjects with statin-associated muscle symptoms and statin-tolerant controls.

MATERIALS & METHODS: Next-generation sequencing was used to characterize the exomes of 76 subjects with severe statin-associated muscle symptoms and 50 statin-tolerant controls.

RESULTS: Twelve probably pathogenic variants were found within the RYR1 and CACNA1S genes in 16% of cases with severe statin-induced myopathy representing a fourfold increase over variants found in statin-tolerant controls. Subjects with probably pathogenic RYR1 or CACNA1S variants had plasma CK 5X to more than 400X the upper limit of normal in addition to having muscle symptoms.

CONCLUSIONS: Genetic variants within the RYR1 and CACNA1S genes are likely to be a major contributor to the susceptibility to statin-associated muscle symptoms.

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