Ruaño Gualberto, Thompson Paul D, Windemuth Andreas, Smith Andrew, Kocherla Mohan, Holford Theodore R, Seip Richard, Wu Alan Hb
Genomas, Inc., 67 Jefferson St., Hartford, CT 06106, USA.
Pharmacogenomics. 2005 Dec;6(8):865-72. doi: 10.2217/14622416.6.8.865.
Statins are highly effective at reducing coronary disease risk. The main side effects of these medications are a variety of skeletal muscle complaints ranging from mild myalgia to frank rhabdomyolysis. To search for physiologic factors possibly influencing statin muscle toxicity, we screened for genetic associations with serum creatine kinase (CK) levels in 102 patients receiving statin therapy for hypercholesteremia. A total of 19 single nucleotide polymorphism (SNPs) were selected from ten candidate genes involved in vascular homeostasis. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. SNPs in the angiotensin II Type 1 receptor (AGTR1) and nitric oxide synthase 3 (NOS3) genes were significantly associated with CK activity. These results demonstrate a strong association between CK activity during statin treatment and variability in genes related to vascular function, and suggest that vascular smooth muscle function may contribute to the muscle side effects of statins.
他汀类药物在降低冠心病风险方面非常有效。这些药物的主要副作用是各种骨骼肌问题，从轻度肌痛到明显的横纹肌溶解。为了寻找可能影响他汀类药物肌肉毒性的生理因素，我们对102例接受他汀类药物治疗高胆固醇血症的患者进行了血清肌酸激酶（CK）水平的基因关联筛查。从涉及血管稳态的10个候选基因中总共选择了19个单核苷酸多态性（SNP）。使用多元线性回归根据关联概率对SNP进行排序，并对最显著的关联进行更详细的分析。血管紧张素II 1型受体（AGTR1）和一氧化氮合酶3（NOS3）基因中的SNP与CK活性显著相关。这些结果表明他汀类药物治疗期间的CK活性与血管功能相关基因的变异性之间存在很强的关联，并表明血管平滑肌功能可能导致他汀类药物的肌肉副作用。
