器官移植受者免疫抑制药物的个体化治疗与药物基因组学研究

摘要

Long-term using of immunosuppressants is necessary to prolong the lifetime of transplanted organ and transplant recipients after transplantation.Due to the great variation in metabolism of immunosuppressive drug,there is the close correlation between drug concentration and rejection or organ injury induced by immunosuppressants.The gene polymorphism of multidrug resistance protein (MDR) and cytochrome P450 isoenzyme (CYP450) could lead to the difference of expression or activation of corresponding coded proteins.Individual gene polymorphism causes not only some special drug metabolism difference,but the huge diversity of the distribution of drug metabolism and drug target function.Except for the clinical therapeutic drug monitoring,detecting hereditary variation and gene polymorphism,analyzing the significance of individual gene polymorphism in drug effect and toxicity,applying individual treatment in clinical treatment research,will be the new mission and challenge for the clinical laboratory technologists.%器官移植为保证移植器官在受者体内生存,需长期使用免疫抑制剂.免疫抑制药物在体内代谢的个体差异大,其血药浓度高低与肝、肾毒性损害和排斥反应密切相关.药物代谢转运蛋白(MDR)和药物代谢细胞色素P450同工酶(CYP450)的基因多态性可导致其编码的蛋白表达或活性呈现多态性,不同个体间对某种特定药物代谢的差异是不同个体编码基因的遗传多态性相互作用的结果,这种相互作用导致药物代谢分布以及药物靶标作用的较大差异.在常规临床血药浓度监测基础上,通过研究药物疗效中的遗传变异,分析个体遗传基因组成在决定药物疗效和代谢毒性的特征,检测个体药物反应遗传基因型和表型或基因多态性,预测个体对药物的治疗剂量已开始逐步应用于药物治疗的临床研究,这是临床检验工作者将面临的新任务与挑战.