RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms
| Autor: | Smitha R. James, Jonathan E. Bard, Paul J. Isackson, Jianxin Wang, Tae Keun Lee, Adrian Levesque, Paul Spurgeon, Norma J. Nowak, Mohammad Zia, Georgirene D. Vladutiu |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Statin Calcium Channels L-Type medicine.drug_class 03 medical and health sciences 0302 clinical medicine Muscular Diseases Genetics medicine Humans Genetic Predisposition to Disease cardiovascular diseases Myopathy Gene Exome sequencing Aged Retrospective Studies Pharmacology RYR1 Aged 80 and over business.industry Malignant hyperthermia Genetic variants nutritional and metabolic diseases Genetic Variation Ryanodine Receptor Calcium Release Channel Middle Aged medicine.disease 030104 developmental biology Case-Control Studies Immunology Molecular Medicine lipids (amino acids peptides and proteins) Female Calcium Channels medicine.symptom Hydroxymethylglutaryl-CoA Reductase Inhibitors business 030217 neurology & neurosurgery Research Article |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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