Zhai Qinglian, van der Lee Maaike, van Gelder Teun, Swen Jesse J
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, Netherlands.
Front Pharmacol. 2022 Jun 16;13:912618. doi: 10.3389/fphar.2022.912618. eCollection 2022.
Cytochrome P450 3A (CYP3A) subfamily enzymes are involved in the metabolism of 40% of drugs in clinical use. Twin studies have indicated that 66% of the variability in CYP3A4 activity is hereditary. Yet, the complexity of the locus and the lack of distinct drug metabolizer phenotypes has limited the identification and clinical application of CYP3A genetic variants compared to other Cytochrome P450 enzymes. In recent years evidence has emerged indicating that a substantial part of the missing heritability is caused by low frequency genetic variation. In this review, we outline the current pharmacogenomics knowledge of CYP3A activity and discuss potential future directions to improve our genetic knowledge and ability to explain CYP3A variability.
细胞色素P450 3A（CYP3A）亚家族酶参与了40%临床使用药物的代谢。双胞胎研究表明，CYP3A4活性66%的变异性是遗传性的。然而，与其他细胞色素P450酶相比，该基因座的复杂性以及缺乏明显的药物代谢表型限制了CYP3A基因变异的识别和临床应用。近年来，有证据表明，部分缺失的遗传力是由低频基因变异引起的。在本综述中，我们概述了目前关于CYP3A活性的药物基因组学知识，并讨论了未来潜在的方向，以提高我们的遗传知识以及解释CYP3A变异性的能力。
