CYP3A5* 3和MDR1基因多态性对造血干细胞移植患者他克莫司浓度及剂量的影响

Effects of CYP3A5* 3 and MDR1 gene polymorphism on concentration and dosage of tacrolimus in allogeneic hematopoietic stem cell transplantation recipients

目的:研究CYP3A5*3和MDR1基因突变对他克莫司血药浓度、单位体表面积剂量、血药浓度/剂量×体表面积(C/D')的影响。方法:采用测序法检测16例异基因造血干细胞移植患者的CYP3A5*3和MDR1 C3435T,G2677T/A,C1236T基因型,比较不同基因型患者之间血药浓度、剂量、C/D'之间的差异。结果:测得CYP3A5*3和MDR1 C3435T,G2677T/A,C1236T的基因突变频率分别为68.75%,43.75%,50%和65.63%。含有CYP3A5*1/*1+*1/*3等位基因的患者,他克莫司初始血药浓度、初始C/D'显著低于CYP3A5*3/*3患者(P<0.05)。MDR1各基因型则无相关性。结论:造血干细胞移植患者CYP3A5*3/*3基因型与他克莫司初始血药浓度、C/D'密切相关。携带CYP3A5*3/*3等位基因的患者服用他克莫司时应减少服药剂量。

Objective： To investigate the effects of CYP3A5 ＊ 3 and MDR1 on the concentration, dosage/ body surface area, and concentration/dosage × body surface area ratios （C/D＇） in allogenie hematopoietie stem cell transplantation （HSCT） patients. Methods： The genotypes of 16 HSCT patients were determined by gene sequencing method. The concentration, dosage, and C/D＇ ratios were compared among all the genotype groups treated with tacrolimus. Results： The frequencies of CYP3A5 ＊ 3 and MDR1 C3435T, G2677T/A, C1236T alleles in HSCT patients were 68.75% , 43.75% , 50% , and 65.63% respectively. The concentration and C/D＇s in patients with CYP3A5 ＊ 1/＊ 1 and ＊ 1/＊ 3 genotypes were significantly lower than those with CYP3A5 ＊ 3/＊ 3 genotype （P 〈 0.05）. No significant association was found among the concentration, dosage, C/D＇s of tacrolimus and MDR1 genotypes. Conclusion： The CYP3A5 ＊ 3/＊ 3 genotype is associated with taerolimus dosage requirement. For the HSCT patients, a decreased dosage regimen will help improve the efficacy of tacrolimus in CYP3A5 ＊ 3/＊ 3 allelic patients.