CYP3A基因多态性与肾移植术后不同时期环孢素浓度剂量个体差异的相关性研究

Effect of CYP3A Polymorphism on Cyclosporine Individual Dosage and Blood Concentration in Renal Transplant Recipients

目的:探讨肾移植受者口服免疫抑制药环孢素(Cs A)浓度剂量的个体差异与代谢酶CYP3A4/5基因多态性的关系。方法:应用连接酶检测反应法分析221例肾移植受者CYP3A4 rs4646437C>T和CYP3A5 6986G>A基因型,考察其对术后服用Cs A后6个月内、6~24个月、超过24个月的Cs A体质量校正剂量谷浓度(C0_/D)和服药2h后浓度(C2/D)的影响。结果:不同CYP3A5 6986G>A基因型移植术后6个月内、6~24个月、24个月后C_0/D均有统计差异(P<0.05),C_0/D值CYP3A56986GG>GA>AA。不同基因型CYP3A4 rs4646437C>T、CYP3A5 6986G>A在移植术后24个月以上C_2/D均有明显差异(P<0.05),C_2/D值CYP3A4 CC>CT>TT,CYP3A5 GG>GA>AA。结论:不同CYP3A5 6986G>A基因型影响移植受者的C_0/D和C_2/D;不同CYP3A4 rs4646437C>T基因型影响移植受者的C_2/D,可作为移植术后Cs A个体化用药的参考指标。移植后用药时间不同,基因型对C_0/D和/或C_2/D的影响也不同。

Objective： To evaluate the correlation of inter-individual variation of cyclosporine dosage and blood concentration and CYP3A4 and CYP3A5 polymorphism in renal transplant recipients. Methods： Two hundred and twenty-one renal transplant recipients treated with eyclosporine were genotyped for CYP3A4 rs4646437C 〉 T and CYP3A5 6986G 〉 A using ligase detection reactions. The effects of genetic polymorphisms of CYP3A4 and CYP3A5 on cyclosporine trough concentration （C0/D） and 2 h post-dQse concentra- tion （C2/D） during the period of 6 months, 6-24 months and above 24 months after renal transplant were studied. Results： CYP3A5 6986G 〉 A genotype affected Co/D during the period of 6 months, 6-24 months and beyond 24 months （ P 〈 0.05 ） with the order of CYP3A5 6986GG 〉 GA 〉 AA. CYP3A4 rs4646437C 〉 T and CYP3A5 6986G 〉 A genotype affected C2/D during the period above 24 months （P 〈 0.05 ） with the order of CYP3A4 rs4646437 CC 〉 CT 〉 TY and CYP3A5 6986GG 〉 GA 〉 AA. Conclusion： CYP3A5 6986G 〉 A genotype affects Co/D and C2/D of cyelosporine, and CYP3A4 rs4646437 C 〉 T genotype affects C2/D of cyelosporine. The effects of genotypes are varied in different stages.