Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Department of Health & Human Services, Research Triangle Park, NC 27709, USA.
Pharmacogenomics. 2020 Mar;21(4):293-306. doi: 10.2217/pgs-2019-0140. Epub 2020 Mar 17.
Fibrates are a medication class prescribed for decades as 'broad-spectrum' lipid-modifying agents used to lower blood triglyceride levels and raise high-density lipoprotein cholesterol levels. Such lipid changes are associated with a decrease in cardiovascular disease, and fibrates are commonly used to reduce risk of dangerous cardiovascular outcomes. As with most drugs, it is well established that response to fibrate treatment is variable, and this variation is heritable. This has motivated the investigation of pharmacogenomic determinants of response, and multiple studies have discovered a number of genes associated with fibrate response. Similar to other complex traits, the interrogation of single nucleotide polymorphisms using candidate gene or genome-wide approaches has not revealed a substantial portion of response variation. However, recent innovations in technological platforms and advances in statistical methodologies are revolutionizing the use and integration of other 'omes' in pharmacogenomics studies. Here, we detail successes, challenges, and recent advances in fibrate pharmacogenomics.
贝特类药物是一种被广泛使用的降脂药物，已被临床应用数十年，用于降低血液中的甘油三酯水平，提高高密度脂蛋白胆固醇水平。这些脂质变化与心血管疾病风险降低有关，贝特类药物常用于降低危险的心血管事件风险。与大多数药物一样，人们早已认识到，贝特类药物的治疗反应存在个体差异，且这种差异具有遗传性。这促使人们研究了药物反应的药物基因组学决定因素，多项研究发现了一些与贝特类药物反应相关的基因。与其他复杂特征一样，使用候选基因或全基因组方法对单核苷酸多态性的检测并未揭示出反应变异的很大一部分。然而，技术平台的最新创新和统计方法学的进步正在彻底改变药物基因组学研究中其他“组学”的使用和整合。在这里，我们详细介绍了贝特类药物药物基因组学的成功、挑战和最新进展。
