Document Detail

Genetic risk factors associated with lipid-lowering drug-induced myopathies.
MedLine Citation:
PMID:  16671104     Owner:  NLM     Status:  MEDLINE    
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.
Georgirene D Vladutiu; Zachary Simmons; Paul J Isackson; Mark Tarnopolsky; Wendy L Peltier; Alexandru C Barboi; Naganand Sripathi; Robert L Wortmann; Paul S Phillips
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Muscle & nerve     Volume:  34     ISSN:  0148-639X     ISO Abbreviation:  Muscle Nerve     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-21     Completed Date:  2006-09-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7803146     Medline TA:  Muscle Nerve     Country:  United States    
Other Details:
Languages:  eng     Pagination:  153-62     Citation Subset:  IM    
Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 936 Delaware Avenue, Buffalo, New York 14209, USA.
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MeSH Terms
AMP Deaminase / deficiency
Aged, 80 and over
Antilipemic Agents / adverse effects*
Carnitine O-Palmitoyltransferase / genetics
DNA Mutational Analysis
Drug Synergism
Fatty Acids / metabolism
Gene Frequency
Glycogen Storage Disease Type V / epidemiology,  genetics
Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
Middle Aged
Muscle, Skeletal / chemistry,  metabolism,  pathology
Muscular Diseases / chemically induced*,  genetics*,  pathology
Risk Factors
Reg. No./Substance:
0/Antilipemic Agents; 0/Fatty Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; EC O-Palmitoyltransferase; EC Deaminase

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