Vladutiu Georgirene D, Simmons Zachary, Isackson Paul J, Tarnopolsky Mark, Peltier Wendy L, Barboi Alexandru C, Sripathi Naganand, Wortmann Robert L, Phillips Paul S
Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 936 Delaware Avenue, Buffalo, New York 14209, USA.
Muscle Nerve. 2006 Aug;34(2):153-62. doi: 10.1002/mus.20567.
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.
降脂药物在高达7%的接受治疗的患者中会产生肌病副作用，严重横纹肌溶解的发生率高达0.5%。潜在的代谢性肌肉疾病尚未得到广泛评估。在一项对136例药物性肌病患者的横断面研究中，我们报告潜在代谢性肌肉疾病的患病率高于一般人群的预期。对照组包括116例接受治疗但无肌病症状的患者、100例从未接触过他汀类药物的无症状普通人群个体以及106例非他汀类药物引起的肌病患者。在110例接受突变检测的患者中，10%为导致三种代谢性肌病的突变杂合子或纯合子，而在接受治疗的无症状患者中，检测呈阳性的比例为3%（P = 0.04）。由于突变纯合子的增加，测试组患者中发现的突变等位基因实际数量比对照组增加了四倍（P < 0.0001）。肉碱棕榈酰转移酶II缺乏症和麦卡德尔病的携带者数量分别比预期的一般人群频率增加了13倍和20倍。肌腺苷酸脱氨酶缺乏症的纯合子增加了3.25倍，携带者状态没有增加。在患者的52%的肌肉活检中，发现线粒体或脂肪酸代谢存在明显的生化异常，31%有多种缺陷。尽管停止治疗，68%的患者仍出现了持续的可变症状。他汀类药物对能量代谢的影响以及对引发肌肉症状的遗传易感性可能是某些高危人群出现肌病结果的原因。
