摘要
目的通过对不同细胞色素P-450 3A5(CYP3A5)基因型的造血干细胞移植及患者外周血中环孢素A(CsA)浓度的比较研究,探讨CYP3A5作为一种预示指标,指导临床个体化应用CsA 的可行性。方法应用聚合酶链反应-限制性片断长度多态性分析(PCR-RFLP)的方法检测患者CYP3A5基因型;采用免疫荧光偏振法监测患者血中CsA浓度。结果在12例样本中,共检测出2 种基因型,其中野生型纯合子2例,杂合子10例。野生型纯合子患者外周血CsA浓度经与杂合子患者相比较,前者谷值浓度(C0)较后者低,相差2.3-6.6倍;服药后2h峰值浓度(C2)亦较后者低,相差1.4-3.8倍。结论CYP3A5基因多态性与造血干细胞移植患者外周血CsA浓度密切相关,在应用CsA之前,通过对患者CYP3A5基因型的检测,有可能指导临床确定其个体化用药的需求量。
Objective To explore the possibility of cytochrome P-450 3A5 (CYP3A5) genotype as a major factor to guide individualized employment of cyclosporin A(CsA) through a comparative study of CsA concentrations in the peripheral blood of hemopoietic stem cell transplant recipients with different CYP3A5 genotypes. Methods Olymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype CYP3A5 gene, and CsA concentrations were detected by a commercial fluorescence polarization immunoassay. Result There were significant differences in CsA concentrations, including standardized trough concentrations C0 and two h peak concentrations C2 , in the two CYP3A5 genotypes found in our samples, and both C0 and C2 in wild homozygotes were lower than heterozygotes. Conclusion CYP3A5 polymorphism is highly associated with CsA concentrations in hemopoietic stem cell transplant recipients, and CYP3A5 genotype may be a predictor to the dose requirement before clinically employment of CsA.
出处
《中华器官移植杂志》
CAS
CSCD
北大核心
2005年第4期207-209,共3页
Chinese Journal of Organ Transplantation
