Srinivasan Shylaja, Yee Sook Wah, Giacomini Kathleen M
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States; Division of Pediatric Endocrinology and Diabetes, University of California, San Francisco, San Francisco, CA, United States.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
Adv Pharmacol. 2018;83:361-389. doi: 10.1016/bs.apha.2018.04.005. Epub 2018 May 14.
Pharmacogenetic studies of antidiabetic drugs have so far focused largely on response to metformin, which is the first-line therapy for treatment of type 2 diabetes (T2D). The first studies of metformin pharmacogenetics were focused on candidate genes that were implicated in metformin pharmacokinetics and transport. Since 2011, genome-wide association studies have been conducted in large cohorts of individuals with T2D identifying genes that are associated with glycemic response to metformin. There have been fewer pharmacogenetic studies of other antidiabetic drugs, and those have been largely limited to candidate gene studies with small sample sizes. Understanding the pharmacogenetics of antidiabetes medications is important for the integration of genetic screening into therapeutic decision making, and to achieve the goal of "precision medicine" for patients with T2D. In this chapter, we provide a review of the pharmacogenetics investigations of metformin and other antidiabetes medications. In addition, we highlight the importance of collaborative efforts with large sample size and representation from multiple ethnic groups in pharmacogenetics studies.
迄今为止,抗糖尿病药物的药物遗传学研究主要集中在对二甲双胍的反应上,二甲双胍是治疗2型糖尿病(T2D)的一线疗法。二甲双胍药物遗传学的首批研究聚焦于与二甲双胍药代动力学和转运相关的候选基因。自2011年以来,已在大量T2D患者队列中开展全基因组关联研究,以确定与二甲双胍血糖反应相关的基因。关于其他抗糖尿病药物的药物遗传学研究较少,且大多局限于小样本量的候选基因研究。了解抗糖尿病药物的药物遗传学对于将基因筛查纳入治疗决策以及实现T2D患者“精准医学”的目标至关重要。在本章中,我们综述了二甲双胍和其他抗糖尿病药物的药物遗传学研究。此外,我们强调了在药物遗传学研究中开展大样本量且涵盖多个种族群体的合作研究的重要性。