钙通道阻滞剂对肾移植患者环孢素血药浓度/剂量的影响与 CYP3A5 基因多态性有关

摘要/Abstract

摘要： 目的: 研究CYP3A5基因多态性对合用钙通道阻滞剂(CCBs)患者环孢素(CsA)血药浓度/剂量(C/D) 的影响。方法: 利用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP) 分析技术对 69例肾移植患者 CYP3A5 基因进行分型, 研究患者在合用CCBs后CsA C/D 的差异及与 CYP3A5 基因型的关系。结果: CYP3A5 基因型为＊1/＊1、＊1/＊3 和＊3/＊3 型的患者分别有8例、23例和38例。肾移植患者的 CYP3A5 A6986G 多态性(CYP3A5＊3) 发生频率为 71.74%。未用CCBs的CYP3A5＊1/＊3 和CYP3A5＊3/＊3 患者其 CsA CD 分别是野生型患者的 1.73 倍和 2.43 倍,CYP3A5 ＊1/＊1、＊1/＊3 型患者在合用 CCBs 前后CsA 的C/D 明显提高( 19.90±7.66 vs 36.01±8.18, 34.33 ±7.87 vs 46.16 ±9.63 ng·mL^-1 per mg·kg^-1;P <0.01, P <0.05) , 而 CYP3A5 ＊3/＊3 型患者CsA的C/D无明显变化(48.27±10.60vs 46.42 ±9.24 ng.mL^-1 per mg·kg^-1)。结论: CCBs对肾移植患者CsA 的 C/D的影响与 CYP3A5基因多态性相关。

关键词: 肾移植, 环孢素, 钙通道阻滞剂, CYP3A5, 基因多态性

Abstract: AIM: To study the relationship be-tween the genetic polymorphism of CYP3A5 gene and the blood concentration/dose ( C/D) ratio of cyclospo-rine combined with calcium channel blockers ( CCBs) in renal transplant patients.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was applied to determine the genotype of CYP3A5 in 69 renal transplant patients. The blood concentration/dose (C/D) ratio of cyclospo-rine was compared in patients coadministrated of CCBs with different genetic polymorphism of CYP3A5.RE-SULTS: The cases of genotype of CYP3A5 ＊1/＊1, CYP3A5＊1/＊3 and CYP3A5 ＊3/＊3 were 8,23 and 38, respectively .The mutation rate of CYP3A5＊ 3 in renal transplant patients was 71.74%.The CsA C/D ratio of patients of CYP3A5＊1/＊1 and CYP3A5 ＊1/＊3were 1 .73 and 2.43 times higher than that in patients of CYP3A5 ＊3/＊3.The CsA C/D ratio of patients ( CYP3A5 ＊1/＊1, CYP3A5 ＊1/＊3) com-binedwith CCBs had been obviously elevated ( 19.90 ±7.66 vs 36.01±8.18, 34.33 ±7.87 vs 46.16± 9.63 ng·mL^-1 per mg·kg^-1 ;P <0.01, P <0.05) , and that of patients with CYP3A5 ＊3/＊3 genotype showed no significant changes ( 48.27 ±10 .60 vs 46.42 ±9.24 ng·mL^-1 per mg·kg^-1 ).CONCLUSION: The CsA C/D ratio is related to the genetic polymorphism of CYP3A5 gene in renal transplant pa-tients combined with CCBs.

Key words: kidney transplantation, cyclosporine, calcium channel blockers, CYP3A5, genetic polymor-phisms

中图分类号:

R969

史道华, 林知捷. 钙通道阻滞剂对肾移植患者环孢素血药浓度/剂量的影响与 CYP3A5 基因多态性有关[J]. 中国临床药理学与治疗学, 2008, 13(10): 1149-1153.

SHI Dao-hua, LIN Zhi-jie. Association between genetic polymorphism of CYP3A5 and blood con-centration/dose ratio of cyclosporine combined with calcium channel blockers in renal transplant patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1149-1153.

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