Eichelbaum Michel, Ingelman-Sundberg Magnus, Evans William E
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Auerbachstr. 112, D-70376 Stuttgart, Germany.
Annu Rev Med. 2006;57:119-37. doi: 10.1146/annurev.med.56.082103.104724.
Pharmacogenetics deals with inherited differences in the response to drugs. The best-recognized examples are genetic polymorphisms of drug-metabolizing enzymes, which affect about 30% of all drugs. Loss of function of thiopurine S-methyltransferase (TPMT) results in severe and life-threatening hematopoietic toxicity if patients receive standard doses of mercaptopurine and azathioprine. Gene duplication of cytochrome P4502D6 (CYP2D6), which metabolizes many antidepressants, has been identified as a mechanism of poor response in the treatment of depression. There is also a growing list of genetic polymorphisms in drug targets that have been shown to influence drug response. A major limitation that has heretofore moderated the use of pharmacogenetic testing in the clinical setting is the lack of prospective clinical trials demonstrating that such testing can improve the benefit/risk ratio of drug therapy.
药物遗传学研究的是个体对药物反应的遗传差异。最广为人知的例子是药物代谢酶的基因多态性，约30%的药物受其影响。如果患者接受标准剂量的巯嘌呤和硫唑嘌呤，硫嘌呤甲基转移酶（TPMT）功能缺失会导致严重的、危及生命的造血毒性。细胞色素P4502D6（CYP2D6）可代谢多种抗抑郁药，其基因重复已被确定为抑郁症治疗反应不佳的一种机制。越来越多的研究表明，药物靶点的基因多态性也会影响药物反应。此前，限制药物遗传学检测在临床应用的一个主要因素是缺乏前瞻性临床试验来证明这种检测能够改善药物治疗的效益/风险比。
