Genetic risk factors associated with lipid-lowering drug-induced myopathies

Georgirene D. Vladutiu, Zachary Simmons, Paul J. Isackson, Mark Tarnopolsky, Wendy L. Peltier, Alexandru C. Barboi, Naganand Sripathi, Robert L. Wortmann, Paul S. Phillips

Research output: Contribution to journalArticle

184 Citations (Scopus)

Abstract

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.

Original languageEnglish (US)
Pages (from-to)153-162
Number of pages10
JournalMuscle and Nerve
Volume34
Issue number2
DOIs
StatePublished - Aug 1 2006

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Muscular Diseases
Lipids
Pharmaceutical Preparations
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Muscles
Metabolic Diseases
Homozygote
Mutation
Glycogen Storage Disease Type V
AMP Deaminase
Population
Deficiency Diseases
Carnitine O-Palmitoyltransferase
Control Groups
Rhabdomyolysis
Genetic Predisposition to Disease
Energy Metabolism
Fatty Acids
Therapeutics
Cross-Sectional Studies

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Vladutiu, G. D., Simmons, Z., Isackson, P. J., Tarnopolsky, M., Peltier, W. L., Barboi, A. C., ... Phillips, P. S. (2006). Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle and Nerve, 34(2), 153-162. https://doi.org/10.1002/mus.20567
Vladutiu, Georgirene D. ; Simmons, Zachary ; Isackson, Paul J. ; Tarnopolsky, Mark ; Peltier, Wendy L. ; Barboi, Alexandru C. ; Sripathi, Naganand ; Wortmann, Robert L. ; Phillips, Paul S. / Genetic risk factors associated with lipid-lowering drug-induced myopathies. In: Muscle and Nerve. 2006 ; Vol. 34, No. 2. pp. 153-162.
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Vladutiu, GD, Simmons, Z, Isackson, PJ, Tarnopolsky, M, Peltier, WL, Barboi, AC, Sripathi, N, Wortmann, RL & Phillips, PS 2006, 'Genetic risk factors associated with lipid-lowering drug-induced myopathies', Muscle and Nerve, vol. 34, no. 2, pp. 153-162. https://doi.org/10.1002/mus.20567

Genetic risk factors associated with lipid-lowering drug-induced myopathies. / Vladutiu, Georgirene D.; Simmons, Zachary; Isackson, Paul J.; Tarnopolsky, Mark; Peltier, Wendy L.; Barboi, Alexandru C.; Sripathi, Naganand; Wortmann, Robert L.; Phillips, Paul S.

In: Muscle and Nerve, Vol. 34, No. 2, 01.08.2006, p. 153-162.

Research output: Contribution to journalArticle

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AU - Isackson, Paul J.

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AU - Phillips, Paul S.

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Vladutiu GD, Simmons Z, Isackson PJ, Tarnopolsky M, Peltier WL, Barboi AC et al. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle and Nerve. 2006 Aug 1;34(2):153-162. https://doi.org/10.1002/mus.20567