University of Chicago, Section of Genetic Medicine and Committee on Clinical Pharmacology and Pharmacogenomics, Division of Biological Sciences, Department of Medicine, Chicago, IL 60637, USA.
Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):17-28. doi: 10.1517/17425250903379546.
An enormous amount of drugs and endogenous substrates are metabolized by the enzymes encoded in the CYP3A gene cluster, making variation at this locus of utmost importance in the field of pharmacogenetics. However, the identification of genetic variation that contributes to the wide phenotypic variability at this locus has been elusive. While dozens of studies have investigated the effects of coding variants, none have found the definitive answer to what variant or variants explain the distribution of enzyme activity and clinical effects seen with the drug metabolized by these genes.
This review highlights the recent pharmacogenetic work at the CYP3A locus, in particular studies on known functional variants in CYP3A4 and CYP3A5. In addition, common pharmacogenetic strategies as well as considerations specific to the CYP3A locus are discussed.
The reader will gain a greater understanding of the complexities involved in studying the CYP3A locus, population differences that may affect pharmacogenetic studies at this locus and the importance of variation that affect gene regulation.
More innovative and comprehensive methods to assay this region are needed, with particular attention paid to the role of gene regulation and non-coding sequence.
大量的药物和内源性底物是由 CYP3A 基因簇编码的酶代谢的，使得该基因座的变异在药物遗传学领域中具有至关重要的意义。然而，鉴定导致该基因座表型变异的遗传变异一直难以捉摸。虽然数十项研究已经调查了编码变异的影响，但没有一项研究能够确定哪种或哪些变异可以解释这些基因代谢的药物的酶活性和临床效果的分布。
本篇综述重点介绍了 CYP3A 基因座的最新药物遗传学研究，特别是关于 CYP3A4 和 CYP3A5 中已知功能变异的研究。此外，还讨论了常见的药物遗传学策略以及 CYP3A 基因座特有的注意事项。
读者将获得对研究 CYP3A 基因座所涉及的复杂性、可能影响该基因座药物遗传学研究的人群差异以及影响基因调控的变异的重要性的更深入的了解。
需要更具创新性和全面的方法来检测该区域，特别要注意基因调控和非编码序列的作用。
