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In a cross\u2010sectional study of 136 patients with drug\u2010induced 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\u2013statin\u2010induced 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 (<jats:italic>P<\/jats:italic> = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (<jats:italic>P<\/jats:italic> &lt; 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\u2010 and 20\u2010fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25\u2010fold 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\u2010risk groups. Muscle Nerve, 2006<\/jats:p>","DOI":"10.1002\/mus.20567","type":"journal-article","created":{"date-parts":[[2006,5,2]],"date-time":"2006-05-02T22:00:43Z","timestamp":1146607243000},"page":"153-162","source":"Crossref","is-referenced-by-count":217,"title":["Genetic risk factors associated with lipid\u2010lowering drug\u2010induced myopathies"],"prefix":"10.1002","volume":"34","author":[{"given":"Georgirene D.","family":"Vladutiu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J.","family":"Isackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Tarnopolsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy L.","family":"Peltier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru C.","family":"Barboi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naganand","family":"Sripathi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Wortmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul S.","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,5,2]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/10408369209114601"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780391113"},{"key":"e_1_2_7_4_2","first-page":"258","article-title":"Statin myopathies: pathophysiologic and clinical perspectives","volume":"24","author":"Baker SK","year":"2001","journal-title":"Clin Invest Med"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.20291"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1258\/000456303322326542"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02522982"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.57.070188.001401"},{"key":"e_1_2_7_9_2","first-page":"218","article-title":"Biochemical and clinical consequences of inhibiting coenzyme Q10 biosynthesis by lipid lowering HMG\u2010CoA reductase inhibitors (statins): a critical overview","volume":"15","author":"Bliznakov EG","year":"1998","journal-title":"Adv Ther"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(93)90211-W"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2001.10719063"},{"key":"e_1_2_7_12_2","first-page":"1095","article-title":"Worsening for using statin in carnitine palmitoyl transferase deficiency myopathy","volume":"38","author":"Delgado\u2010Lopez F","year":"2004","journal-title":"Rev Neurol"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)80130-3"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.SMJ.0000061501.81880.83"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe048326"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1995.tb01912.x"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0202.101971"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002280000248"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1993.tb03948.x"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.292.21.2585"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)00442-7"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.7.923"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199405000-00004"},{"key":"e_1_2_7_24_2","volume-title":"IMSHealth Annual TRX","year":"2003"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.93.279"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.03.002"},{"key":"e_1_2_7_27_2","first-page":"517","article-title":"Serum and muscle ubiquinone levels in healthy subjects","volume":"125","author":"Laaksonen R","year":"1995","journal-title":"J Lab Clin Med"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(97)89180-1"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000055089.39373.FC"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1258\/0004563041201554"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)36985-6"},{"key":"e_1_2_7_32_2","first-page":"95","article-title":"Palmityl\u2010CoA. 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