肝移植受者CYP3A5基因多态性对他克莫司血药浓度与剂量比值的影响

目的 研究CYP3A5基因多态性对肝移植受者术后他克莫司血药浓度与剂量比值（C/D比值）的影响.方法 选取2011年1月至2012年12月在上海交通大学医学院附属仁济医院肝脏外科接受原位肝移植术的86例受者,记录其术后1,2周和1,2,3,6个月他克莫司剂量,并测定相应时间点的他克莫司血药谷浓度,计算他克莫司C/D比值.检测肝移植受者CYP3A5基因多态性,观察不同基因型对他克莫司C/D比值的影响.结果 86例受者中,5例为CYP3A5＊1/＊1型（5.8%）,38例为CYP3A5＊1/＊3型（44.2%）,43例为CYP3A5＊3/＊3型（50%）.受者术后1,2周和1,2,3个月他克莫司C/D比值与CYP3A5基因型明显相关,携带CYP3A5＊1等位基因受者的C/D比值低于CYP3A5＊3/＊3型受者,差异有统计学意义（P〈0.05）.结论 CYP3A5基因多态性是影响肝移植受者术后他克莫司血药浓度的重要遗传因素.CYP3A5＊1/＊1型和CYP3A5＊1/＊3型受者需要比CYP3A5＊3/＊3型受者服用更高剂量的他克莫司才能达到相似的血药浓度.用药前检测受者基因型可以更有效地对他克莫司进行剂量调整.

Effect of CYP3A5 polymorphism on the concentration/dose ratio of tacrolimus in liver transplant recipients

Objective To investigate the effect of CYP3A5 polymorphism on the concentration/ dose （C/D） ratio of tacrolimus in liver transplant recipients. Methods Eighty-six liver transplant recipients from January 2011 to December 2012 who received tacrolimus treatment in our hospital were collected. At 1, 2, 4, 8, 12, and 24 weeks after transplantation, tacrolimus doses, its trough blood levels, and the C/D ratio were recorded and calculated. The CYP3A5 genotypes were determined by the PCR-RFLP method. The C/D ratio of tacrolimus was compared in different genotype recipients. Results The number of CYP3A5＊ 1/＊ 1, ＊1/＊ 3 and ＂3/＊ 3 allelic gene was 5（5. 8%）, 38（44.2% ）, and 43（50% ）. At 1, 2, 4, 8, and 12 weeks after transplantation,the C/D ratio of taerolimus had positive correlation with the CYP3A5 genotype of recipients. The recipient with CYP3A5 ＊ 1 allelic genes had statistically significant lower C/D ratio than those with CYP3A5 ＊ 3 allelic genes did （ P 〈 0.05 ）. Conclusions CYP3A5 polymorphism is the important hereditary factor for the concentration of tacrolimus in liver transplant recipients. The recipients with CYP3A5 ＊ 1 allelic genes need higher dose of tacrolimus to achieve the perfect concentration. Clinical application of pharmacogenetic studies will be significant for individualization of tacrolimus dosage.