Faculty Collaboration Database

Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006 Aug;34(2):153-62

Date

05/04/2006

Pubmed ID

16671104

DOI

10.1002/mus.20567

Scopus ID

2-s2.0-33746665298 (requires institutional sign-in at Scopus site)   217 Citations

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.

Author List

Vladutiu GD, Simmons Z, Isackson PJ, Tarnopolsky M, Peltier WL, Barboi AC, Sripathi N, Wortmann RL, Phillips PS

Author

Wendy L. Peltier MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

AMP Deaminase
Adult
Aged
Aged, 80 and over
Carnitine O-Palmitoyltransferase
DNA Mutational Analysis
Drug Synergism
Fatty Acids
Female
Gene Frequency
Glycogen Storage Disease Type V
Heterozygote
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Male
Middle Aged
Muscle, Skeletal
Muscular Diseases
Risk Factors