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目的探讨异基因造血干细胞移植(HSCT)患者中CYP3A4~*18B和MDR1 C3435T基因多态性与他克莫司血药浓度、稳态剂量和不良反应之间的关系。方法采用直接测序法检测CYP3A4~*18B和MDR1 C3435T基因型,比较不同基因型患者之间他克莫司初始血药浓度/剂量×体表面积(ρ_0/D_0’)、稳态剂量/体表面积(D’)及不良反应发生率的差异。结果 16例HSCT患者CYP3A4~*18B和MDR1 C3435T等位基因突变频率分别为34.38%和43.75%。CYP3A4~*1/~*1基因型患者他克莫司初始ρ_0/D_0’明显高于~*18B等位基因携带者(P<0.05);稳态时D’显著低于~*18B等位基因携带者(P<0.05)。MDR1 C3435T TT型患者C0/D0’、D’与C等位基因携带者相比差异无统计学意义(P>0.05)。CYP3A4~*18B和MDR1 C3435T基因多态性与急性移植物抗宿主病及他克莫司所致不良反应无关(P>0.05)。结论 HSCT患者CYP3A4~*18B基因多态性与他克莫司的ρ_0/D_0’、D’相关。
Objective To investigate the relationship between CYP3A4 ~ * 18B and MDR1 C3435T gene polymorphism and tacrolimus plasma concentration, steady-state dose and adverse reactions in patients with allogeneic hematopoietic stem cell transplantation (HSCT). Methods The CYP3A4 ~ * 18B and MDR1 C3435T genotypes were detected by direct sequencing. The initial tacrolimus plasma concentration / dose × body surface area (ρ_0 / D_0 ’), steady state dose / body surface area ( D ’) and the incidence of adverse reactions. Results The frequencies of CYP3A4 ~ * 18B and MDR1 C3435T alleles in 16 HSCT patients were 34.38% and 43.75%, respectively. The initial ρ_0 / D_0 ’of tacrolimus in CYP3A4 ~ * 1 / ~ * 1 genotype was significantly higher than that in the * 18B allele (P <0.05); at steady state, D’ was significantly lower than the * 18B allele Gene carriers (P <0.05). There was no significant difference in C0 / D0 ’, D’ and C allele between MDR1 C3435T and TT genotype TT patients (P> 0.05). The polymorphisms of CYP3A4 ~ * 18B and MDR1 C3435T were not associated with acute graft versus host disease and adverse reactions caused by tacrolimus (P> 0.05). Conclusion CYP3A4 ~ * 18B polymorphism in HSCT patients is related to ρ_0 / D_0 ’and D’ of tacrolimus.