Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies

Georgirene D. Vladutiu, Paul J. Isackson, Kenneth Kaufman, John B. Harley, Beth Cobb, Lisa Christopher-Stine, Robert L. Wortmann

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalMolecular genetics and metabolism
Volume104
Issue number1-2
DOIs
StatePublished - Sep 1 2011

Keywords

  • Coexisting genetic risk
  • Malignant hyperthermia
  • Metabolic muscle disease
  • RYR1 gene mutations
  • Statin myopathy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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  • Cite this

    Vladutiu, G. D., Isackson, P. J., Kaufman, K., Harley, J. B., Cobb, B., Christopher-Stine, L., & Wortmann, R. L. (2011). Genetic risk for malignant hyperthermia in non-anesthesia-induced myopathies. Molecular genetics and metabolism, 104(1-2), 167-173. https://doi.org/10.1016/j.ymgme.2011.07.001