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Genetic risk factors associated with lipid‐lowering drug‐induced myopathies
Author(s) -
Vladutiu Georgirene D.,
Simmons Zachary,
Isackson Paul J.,
Tarnopolsky Mark,
Peltier Wendy L.,
Barboi Alexandru C.,
Sripathi Naganand,
Wortmann Robert L.,
Phillips Paul S.
Publication year - 2006
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20567
Subject(s) - asymptomatic , medicine , population , rhabdomyolysis , myopathy , gastroenterology , muscle biopsy , endocrinology , mitochondrial myopathy , biopsy , mitochondrial dna , biology , genetics , environmental health , gene
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. Muscle Nerve, 2006