Department of Pediatrics, University of California San Francisco, Oakland, CA, USA.
Departments of Pediatrics and Medicine, University of California San Francisco, Oakland, CA, USA.
Pharmacogenomics. 2021 May;22(7):413-421. doi: 10.2217/pgs-2020-0197. Epub 2021 Apr 16.
Although statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) have proven effective in reducing plasma low-density lipoprotein levels and risk of cardiovascular disease, their lipid lowering efficacy is highly variable among individuals. Furthermore, statin treatment carries a small but significant risk of adverse effects, most notably myopathy and new onset diabetes. Hence, identification of biomarkers for predicting patients who would most likely benefit from statin treatment without incurring increased risk of adverse effects can have a significant public health impact. In this review, we discuss the rationale for the use of subject-derived lymphoblastoid cell lines in studies of statin pharmacogenomics and describe a variety of approaches we have employed to identify novel genetic markers associated with interindividual variation in statin response.
虽然他汀类药物(3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂)已被证明可有效降低血浆低密度脂蛋白水平并降低心血管疾病风险,但它们在个体中的降脂效果差异很大。此外,他汀类药物治疗具有较小但显著的不良反应风险,最常见的是肌病和新发糖尿病。因此,识别生物标志物来预测最有可能从他汀类药物治疗中获益而不会增加不良反应风险的患者,可能会对公共健康产生重大影响。在这篇综述中,我们讨论了在他汀类药物药物基因组学研究中使用源自个体的淋巴母细胞系的原理,并描述了我们采用的各种方法来识别与他汀类药物反应个体间差异相关的新的遗传标记。