Paul J Isackson1, Jianxin Wang2, Mohammad Zia2, Paul Spurgeon2, Adrian Levesque2, Jonathan Bard2, Smitha James3, Norma Nowak3,4, Tae Keun Lee1, Georgirene D Vladutiu1,5. 1. Department of Pediatrics, State University of New York at Buffalo, NY 14203, USA. 2. Center for Computational Research, State University of New York at Buffalo, NY 14203, USA. 3. New York State Center of Excellence in Bioinformatics & Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA. 4. Department of Biochemistry, Jacobs School of Medicine & Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA. 5. Departments of Neurology & Pathology & Anatomical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
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.
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.
Authors: Katrin Sangkuhl; Robert T Dirksen; Maria L Alvarellos; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2020-02 Impact factor: 2.000
Authors: William A Murphy; Nan Lin; Amy Damask; Gregory G Schwartz; P Gabriel Steg; Michael Szarek; Poulabi Banerjee; Sergio Fazio; Garen Manvelian; Robert Pordy; Alan R Shuldiner; Charles Paulding Journal: Circ Genom Precis Med Date: 2022-05-11