Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8344243 | Molecular Genetics and Metabolism | 2011 | 7 Pages |
Abstract
Malignant hyperthermia (MH) is a pharmacogenetic, autosomal dominantly inherited disorder of skeletal muscle triggered by volatile anesthetics and infrequently by extreme exertion and heat exposure. MH has variable penetrance with an incidence ranging from 1 in 5000 to 1 in 50,000-100,000 anesthesias. Mutations in the ryanodine receptor gene, RYR1, are found in 50-70% of cases. We hypothesized that a portion of patients with drug-induced muscle diseases, unrelated to anesthesia, such as severe statin myopathy, have underlying genetic liability that may include RYR1 gene mutations. DNA samples were collected from 885 patients in 4 groups: severe statin myopathy (n = 197), mild statin myopathy (n = 163), statin-tolerant controls (n = 133), and non-drug-induced myopathies of unknown etiology characterized by exercise-induced muscle pain and weakness (n = 392). Samples were screened for 105 mutations and variants in 26 genes associated with 7 categories of muscle disease including 34 mutations and variants in the RYR1 gene. Disease-causing mutations or variants in RYR1 were present in 3 severe statin myopathy cases, 1 mild statin myopathy case, 8 patients with non-drug-induced myopathy, and none in controls. These results suggest that disease-causing mutations and certain variants in the RYR1 gene may contribute to underlying genetic risk for non-anesthesia-induced myopathies and should be included in genetic susceptibility screening in patients with severe statin myopathy and in patients with non-statin-induced myopathies of unknown etiology.
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Authors
Georgirene D. Vladutiu, Paul J. Isackson, Kenneth Kaufman, John B. Harley, Beth Cobb, Lisa Christopher-Stine, Robert L. Wortmann,