CYP3A5基因多态性检测对肝移植患者术后他克莫司用药的指导作用

Instruction effect of of CYP3A5 gene polymorphism on tacrolimus dosage after liver transplantation

目的探讨CYP3A5基因多态性检测对肝移植患者术后他克莫司(FK506)用药的指导作用。方法选择接受原位肝移植术的患者67例,采用DNA直接测序法检测患者CYP3A5基因多态性,计算肝移植术后1周、2周、1个月患者每千克体质量每天的FK506剂量(D),采用ELISA法检测各时点全血FK506谷浓度,计算浓度/剂量比值(C/D)。结果 67例肝移植患者中,CYP3A5*1/*1基因型15例(22.4%),CYP3A5*1/*3基因型23例(34.3%),CYP3A5*3/*3基因型29例(43.3%)。CYP3A5*3/*3基因型肝移植患者术后1周、2周、1个月FK506的C/D值显著高于CYP3A5*1/*1、CYP3A5*1/*3基因型(P均<0.05)。结论 CYP3A5*3/*3基因型较CYP3A5*1/*1、CYP3A5*1/*3基因型肝移植患者术后应用FK506达到血药浓度所需剂量更低,检测患者CYP3A5基因多态性有助于肝移植术后FK506的个性化治疗。

Objective To evaluate the instruction effect of CYP3A5 gene polymorphisms on tacrolimus dosage adjusted trough blood concentration during the early period after liver transplantation in patients. Methods 67 liver transplantation recipients were genotyped by DNA sequencing for CYP3AS. Taerolimus whole blood levels were measured by enzymelinked immunospecific assay. Dose-adjusted trough blood concentrations （C） were determined and compared among different genotype groups. Results The CYP3A5 ＊ 1/＊ 1 was observed in 15 subjects （22.4%）, 23 （34.3%） carried ＊ 1/ ＊ 3, and 29 （43.3%） carried ＊ 3/＊ 3. CYP3A5 ＊ 3/＊ 3 variant was associated with significant higher taerolimus dose at 1 week, 2 week and 1 month after transplantation. The tacrolimus C/D ratios were obviously higher in recipients carrying CYP3A5 ＊ 3/＊ 3. Conclusions Genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of tacrolimus pharmacokinetics during the early period after liver transplantation in patients. Patients in CYP3A5 non-expressors require a low dose of tacrolimus to reach target levels compared with expressors, comparing with patients carrying CYP3A5 ＊ 1/1 ,CYP3A5 ＊ 3/3.