Neary M, Owen A
a Infection Pharmacology Group , University of Liverpool , Liverpool , UK.
Expert Opin Drug Metab Toxicol. 2017 Nov;13(11):1169-1181. doi: 10.1080/17425255.2017.1391214. Epub 2017 Oct 16.
Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A enzymes, CYP2C enzymes, UGT2 enzymes, ABCB1, ABCC2, SLCO1B1, NR1I2, and NR1I3 that have previously been associated with variability in antiretroviral pharmacokinetics. Additionally, the impact of ethnicity in these pharmacogenetics studies is discussed, and variation in findings between different ethnic groups is reviewed. A literature search of relevant published work was conducted between April 2017 and September 2017 utilizing the following databases: PubMed, Google Scholar, Web of Science, and Ensembl. Keywords used included drug name, rs (SNP identifier) number, and known effect (if applicable). This report highlights the variation observed between different ethnic populations and subsequently the importance of stratification within pharmacogenetic studies. Expert opinion: Utilization of these findings in future pharmacogenetics studies would aid in the understanding of the extent and impact of genetic variants in different populations and the consequences this has for achieving sustained virological response to antiretroviral therapy.
人类基因组序列的变异有时在药代动力学和/或药效学中发挥重要作用。先前的研究表明,不同种族群体之间以及群体内部都存在高度变异。涵盖领域:本综述旨在总结CYP2B6、CYP3A酶、CYP2C酶、UGT2酶、ABCB1、ABCC2、SLCO1B1、NR1I2和NR1I3中的关键单核苷酸多态性(SNP),这些SNP先前已被证明与抗逆转录病毒药物的药代动力学变异性相关。此外,还讨论了种族在这些药物遗传学研究中的影响,并综述了不同种族群体之间研究结果的差异。2017年4月至9月期间,利用以下数据库对相关已发表的研究进行了文献检索:PubMed、谷歌学术、科学网和Ensembl。使用的关键词包括药物名称、rs(SNP标识符)编号和已知效应(如适用)。本报告强调了不同种族群体之间观察到的变异,以及随后在药物遗传学研究中进行分层的重要性。专家观点:在未来的药物遗传学研究中利用这些发现将有助于理解不同人群中基因变异的程度和影响,以及这对实现抗逆转录病毒治疗的持续病毒学应答的影响。