Dubovsky Steven L
University at Buffalo, Department of Psychiatry , 462 Grider St, Buffalo, NY 14215 , USA +1 716 898 5940 ; +1 716 898 4538 ;
Expert Opin Drug Metab Toxicol. 2015 Mar;11(3):369-79. doi: 10.1517/17425255.2015.998996. Epub 2015 Jan 2.
Pharmacogenomics, which is derived from genome-wide association studies (GWAS), and pharmacogenetics, which involves candidate gene association studies (CGASs), are proving increasingly useful in personalized cancer care. Research in psychiatric applications has primarily involved genetic polymorphisms of P450 CYP enzymes, which mediate oxidative metabolism, particularly CYP2D6, which is involved in the metabolism of at least 30 psychotropic medications. This work has been supplemented by genotyping of proteins for the drug efflux pump P-glycoprotein (P-gp), serotonin receptors, and the serotonin reuptake pump.
This review covers principles of pharmacogenetics and pharmacogenomics, previous analyses of pharmacokinetic and pharmacodynamics studies, newer studies of the predictive value of genetic testing in the treatment of depression, obstacles to implementation of genetic testing in predicting treatment response and side effects, and suggestions for future research.
Studies of multiple genes have produced some positive results in groups of patients, but genetic testing does not yet seem to be applicable to choosing medications for a specific patient.
源自全基因组关联研究(GWAS)的药物基因组学以及涉及候选基因关联研究(CGASs)的药物遗传学,在个性化癌症护理中日益显示出其有用性。精神病学应用方面的研究主要涉及介导氧化代谢的P450 CYP酶的基因多态性,尤其是参与至少30种精神药物代谢的CYP2D6。这项工作通过对药物外排泵P-糖蛋白(P-gp)、5-羟色胺受体和5-羟色胺再摄取泵的蛋白质进行基因分型得到了补充。
本综述涵盖药物遗传学和药物基因组学的原理、既往药代动力学和药效学研究分析、基因检测在抑郁症治疗中预测价值的最新研究、基因检测在预测治疗反应和副作用方面实施的障碍以及对未来研究的建议。
对多基因的研究在患者群体中取得了一些积极成果,但基因检测似乎尚未适用于为特定患者选择药物。