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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 investigate the relationship between individual differences in dose of cyclosporine (Cs A) and metabolic CYP3A4 / 5 polymorphism in kidney transplant recipients. Methods: The genotypes of CYP3A4 rs4646437C> T and CYP3A5 6986G> A in 221 renal transplant recipients were analyzed by ligase assay. The levels of CYP3A5 6986G> A in 6 months, 6-24 months, more than 24 months Monthly Cs A body weight correction dose trough concentration (C0_ / D) and 2h after taking the drug concentration (C2 / D). Results: The C_0 / D of CYP3A5 6986G> A genotype were statistically different (P <0.05) and C_0 / D of CYP3A56986GG> GA> AA within 6 months after 6-24 months and 24 months after transplantation. The C_2 / D of CYP3A4 rs4646437C> T and CYP3A5 6986G> A in different genotypes were significantly different at 24 months after transplantation (P <0.05), C_2 / D values of CYP3A4 CC> CT> TT, CYP3A5 GG> GA> . CONCLUSION: Different genotypes of CYP3A5 6986G> A affect C_0 / D and C_2 / D of transplanted recipients. Different genotypes of CYP3A4 rs4646437C> T affect C_2 / D of transplant recipients, which can be used as reference for personalized CsA after transplantation index. The different medication time after transplantation, the effect of genotype on C_0 / D and / or C_2 / D is also different.