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. 2018 Nov;19(16):1235-1249.
doi: 10.2217/pgs-2018-0106. Epub 2018 Oct 16.

RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms

Paul J Isackson  1 , Jianxin Wang  2 , Mohammad Zia  2 , Paul Spurgeon  2 , Adrian Levesque  2 , Jonathan Bard  2 , Smitha James  3 , Norma Nowak  3   4 , Tae Keun Lee  1 , Georgirene D Vladutiu  1   5
Affiliations

RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms

Paul J Isackson et al. Pharmacogenomics. 2018 Nov.

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.

Keywords: RYR1; exome sequencing; malignant hyperthermia; myopathy; statin.

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Conflict of interest statement

Financial & competing interests disclosure

This work was supported by grants from the John R Oishei Foundation; an Interdisciplinary Research and Creative Activities Award from the University at Buffalo's Office of the Vice President for Research; NIH grants R01 HL085800; R21 AR055704; the Paul E Rich Jr & Doris Miller Rich Fund and by the New York State Center of Excellence in Bioinformatics and Life Sciences at the University of Buffalo. We acknowledge the help of UB's Genomics and Bioinformatics Core and the Buffalo Institute for Genomics and Data Analytics. Whole exome sequencing services were provided by the Northwest Genomics Center at the University of Washington, Department of Genome Sciences, under US Federal Government contract number HHSN268201100037C from the NIH, National Heart, Lung, and Blood Institute. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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