CYP3A5和MDR1基因多态性与肝移植病人他克莫司浓度/剂量比的关系

 目的研究肝移植术后患者的细胞色素P4503A5酶(CYP3A5)和多药耐药蛋白(MDR1)基因多态性对他克莫司浓度/剂量比的影响。方法记录患者的体重、他克莫司剂量和血药浓度等指标,采用聚合酶链式反应-限制性内切片段长度多态性(PCR-RFLP)方法对肝移植患者进行基因分型,比较不同基因型患者之间他克莫司的浓度/剂量比。结果CYP3A5*1/*1和*1/*3型患者的他克莫司浓度/剂量比明显低于*3/*3型患者(P<0.01),MDR1的3435和2677位点各基因型分组之间无明显差异(P>0.05)。结论CYP3A5基因*3多态性与他克莫司血药浓度/剂量比具有显著相关性,*1/*1和*1/*3型的患者拟取得相似的血药浓度要比*3/*3型患者服用更高剂量的他克莫司,用药前检测基因型可以更有效地对他克莫司进行剂量调整。

Effect of CYP3A5 and MDR1 Gene Polymorphism on Concentration/Dose Ratios of Tacrolimus in Chinese Liver Transplant Patients

OBJECTIVE To investigate the effect of CYP3A5 and MDR1 on the concentration/dose ratio of tacrolimus in Chinese liver transplant patients. METHODS Blood samples were collected from liver transplant patients who received tacrolimus . The CYP3A5 and MDR1 genotypes were determined by PCR-RFLP method. Tacrolimus tough concentration was measured by FPIA. The concentration/dose ratio was determined at 7,14 d and 1 month after liver transplantation. RESULTS The concentration/dose ratios of patients with CYP3A5*1/*1 and CYP3A5 *1/*3 carrier were significantly lower than those with CYP3A5*3*3 patients at 7,14 d and 1 month after liver transplantation. No difference was found among the MDR1 genotypes. CONCLUSION CYP3A5 *3 polymorphism is correlated with the whole blood concentration/dose ratio in Chinese liver transplant patients. Clinical application of pharmacogenetic studies will be significant for the individualization of tacrolimus dosage.