肾移植受者硫嘌呤甲基转移酶基因多态性与硫唑嘌呤不良反应关系的研究

Research on the relationship between thiopurine S-methyltransferase genetic polymorphisms and azathioprine adverse drug reactions in patients with kidney transplantation

目的:探讨硫嘌呤甲基转移酶(thiopurine S-methyltransferase,TPMT)表型和基因多态性与硫唑嘌呤(AZA)所致不良反应的关系。方法:应用高效液相色谱法(HPLC)测定150例肾移植患者红细胞TPMT活性,采用等位基因特异性的PCR和限制性片断长度多态性的方法检测TPMT*2、*3A、*3B和*3C四种基因型,分析TPMT活性和基因多态性与AZA所致不良反应的关系。结果:30例(20%)患者由于发生了不良反应而停用AZA或减少了AZA的用量,其中12例患者发生了血液毒性,另外18例发生了肝脏毒性。将未发生不良反应的患者作为对照组,其红细胞TPMT活性范围为16.63~68.25 U,平均为(38.43±11.59)U。发生了血液毒性的患者红细胞TPMT活性平均为(24.16±9.84)U,明显低于未发生不良反应的患者(P=0.0003)。另外18例发生了肝脏毒性的患者TPMT活性离散度较大,与对照组比较差异无统计学意义(P=0.145)。本研究未发现TPMT活性缺乏者。共发现7例(4.7%)TPMT*3C杂合子患者,这7例患者均为TPMT中等活性13.04~19.21 U,平均为(...

AIM: To investigate the relationship between thiopurine S-methyltransferase(TPMT) polymorphisms and azathioprine(AZA) adverse effects in patients with kidney transplantation.METHODS: The erythrocyte TPMT activity of 150 patients with kidney transplantation was detected by high performance liquid chromatography(HPLC).The TPMT*2,*3A,*3B and *3C four kinds of genetype were determined by allele specific PCR and PCR-restriction fragment length polymorphism.The relationship of the activity,gene polymorphism,adver...