CYP3A4*18B基因多态性与他克莫司血药浓度的相关性研究

目的:探讨中国汉族肾移植患者CYP3A 4* 18B基因型对术后1个月内他克莫司谷浓度的影响.方法:采用限制性片段长度多态性技术分析了30例汉族患者CYP3A4* 18B基因型,采用酶增强免疫测定技术测定患者他克莫司谷浓度.将血药浓度标准化后对不同基因型患者剂量调整谷浓度差异进行t检验.结果:测得CY P3A 4*18B等位基因频率为0.333,符合Hardy-Weinberg平衡.将患者分成*1/*1型慢代谢组和*1/*18B合并*18B/*18B型快代谢组,两组标准化谷浓度分别为(98.02±18.56) ng·kg·mL-1· mg-1和(62.91±18.15) ng· kg· mL-1· mg-1 (P＜0.01),慢代谢组的FK506剂量调整谷浓度显著高于快代谢组.结论:CYP3A 4* 18B基因多态性与他克莫司剂量调整谷浓度显著相关,该突变可能导致CYP3A4酶活性的提高.

Association between CYP3A4*18B Polymorphisms and Serum Tacrolimus Concentrations

Objective: To approach the effect of CYP3A4*18B genetic polymorphisms on serum tacrolimus(FK506) trough concentrations(C0) in Chinese Han renal transplant patients during the first month after transplantation.Methods: A total of 30 renal transplant recipients receiving FK506 were genotyped by PCR-RFLP.The C0 of FK506 were determined by EMIT.A t-test was employed to analyze the relationship between CYP3A4*18B genotype and dose-adjusted C0 of FK506.Results: The allele frequency of CYP3A4*18B was 0.333 and it fitted Hardy-Weinberg equilibrium.Patients were classified into 2 groups: poor metabolizer(PM) homozygous for *1/*1 and extensive metabolizer(EM) hetero-or homozygous for *1/*18B or *18B/*18B.The dose-adjusted C0 of the 2 groups were(98.02±18.56) ng·kg·mL-1·mg-1 and(62.91±18.15) ng·kg·mL-1·mg-1(P<0.01),respectively.The FK506 dose-adjusted C0 of the PM group were significantly higher than those of the EM group.Conclusion: The data suggest that the CYP3A4*18B genotype affects FK506 dose-adjusted C0 probably resulting from a higher CYP3A4 enzymatic activity of this mutation in Chinese renal transplant patients.