RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms. (16th October 2018)

• Record Type: Journal Article
• Authors: Isackson, Paul J; Wang, Jianxin; Zia, Mohammad; Spurgeon, Paul; Levesque, Adrian; Bard, Jonathan; James, Smitha; Nowak, Norma; Lee, Tae Keun; Vladutiu, Georgirene D
• Is Part Of: Pharmacogenomics. Volume 19:Number 16(2018)
• Page Start: 1235
• Page End: 1249
• Publication Date: 2018-10-16
• Subjects: exome sequencing -- malignant hyperthermia -- myopathy -- RYR1 -- statin; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2018-0106
• Languages: English
• ISSNs: 1462-2416

Abstract

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: 12 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.