供受体CYP3A5基因多态性与肝移植患者术后他克莫司浓度/剂量比的关系

Effect of CYP3A5 polymorphism in the donor or recipient on the concentration/dose ratio of tacrolimus in liver transplant patients

目的研究肝移植供、受体CYP3A5基因多态性对受者术后他克莫司浓度/剂量比的影响。方法研究对象为2009年2月至6月期间在中山大学附属第三医院肝移植中心接受肝移植手术的32例受者及其对应供体。记录患者术后1周、2周、4周、12周他克莫司用量,并测定相应时间点的他克莫司谷浓度值,计算他克莫司浓度/剂量比。采用聚合酶链反应-限制性内切酶片段长度多态性方法对肝移植供、受体进行CYP3A5基因分型,比较不同基因型对受者术后他克莫司浓度/剂量比的影响。结果供、受者基因型分布比较差异均无统计学意义(P>0.05)。CYP3A5*3等位基因总发生频率为76%(97/128),CYP3A5*1等位基因总发生频率为24%(31/128)。受者术后2、4、12周他克莫司浓度/剂量比与供体CYP3A5基因型明显相关,与供体为携带*3/*3基因型的受者比较,供体为*1/*1和*1/*3基因型的受者该值明显降低,比较差异有统计学意义(均为P<0.05),后两者比较差异无统计学意义(P>0.05)。术后1、2、4、12周,不同CYP3A5基因型受体的他克莫司浓度/剂量比比较,差异均无统计学意义(均为P>0.05)。结论供体CYP3A5基因多态性是影响肝移植术后患者他克莫司血药浓度的重要遗传因素。供体携带*1等位基因,其受者需更高剂量他克莫司才能达到目标血药浓度。

Objective To investigate the effect of CYP3A5 polymorphism in the donor or recipient on the concentration/dose ratio of tacrolimus in liver transplant patients.Methods The study subjects were collected from liver transplant recipients who received tacrolimus and corresponding donors in the Third Affiliated Hospital of Sun Yat-sen University,from February to June 2009.At 1,2,4 and 12 weeks after transplantation,tacrolimus doses,trough blood levels and concentration /dose ratio were determined.The CYP3A5 genotypes were determined by polymerase chain reaction（PCR）-restriction fragment length polymorphism（RFLP）method.The concentration /dose ratio of tacrolimus was compared in different genotype recipients after transplantation.Results No significant difference was found in the genotype of donors and recipients（P0.05）.The frequency of CYP3A5＊3 allelic gene was 76 %（97/128）and the frequency of CYP3A5＊1 allelic gene was 24 %（31/128）.At 2,4 and 12 weeks after transplantation,the concentration/dose ratios of tacrolimus in recipients had positive correlation with the CYP3A5 genotype in donors.The concentration /dose ratios of recipients with CYP3A5＊1 /＊1 and CYP3A5＊1/3 donors were significantly lower than those of recipients with CYP3A5＊3/＊3 genotype donors（all in P0.05）.No significant different was found between the concentration/dose ratios of recipients with CYP3A5＊1 /＊1 and CYP3A5＊ 1/＊3 donors（P0.05）.And no significant was found in the concentration/dose ratios of different CYP3A5 genotypes recipients at 1,2,4 and 12 weeks after liver transplantation（all in P0.05）.Conclusion CYP3A5 polymorphism in the donors is an important hereditary factor in the concentration of tacrolimus in liver transplant recipients.The recipients with＊ 1 allelic gene donors need higher dose of tacrolimus to achieve the perfect concentration.