肾移植术后他克莫司神经毒性与CYP3A5基因多态性的相关性研究

Correlation between tacrolimus neurotoxicity and CYP3A5 polymorphism after renal transplantation

目的总结CYP3A5基因多态性检测与肾移植患者术后他克莫司神经系统毒性的相关性。方法回顾性分析我院2017年至2020年116例肾移植术后应用他克莫司的患者。采用DNA直接测序法检测患者CYP3A5基因多态性,观察不同基因的患者术后不同时间段的他克莫司药物浓度及神经毒性反应。结果肾移植术后使用他克莫司的患者神经毒性反应的发生率达38%,116例肾移植患者中,CYP3A5*3/*3基因型肾移植患者术后2周内的他克莫司血药浓度低于CYP3A5*1/*1、CYP3A5*1/*3基因型的患者,2周后及长期的血药浓度则高于CYP3A5*1/*1、CYP3A5*1/*3基因型的患者,发生神经毒性反应的概率也更高。结论他克莫司血药浓度的高低是引起肾移植术后早期神经系统并发症的重要影响因素。CYP3A5*3/*3基因型的患者为慢代谢型,发生神经毒性反应的概率也更高。较另外2个基因型服用相同剂量他克莫司2周后的血药浓度更高,所需剂量应该减低。

Objective Summarize the correlation between the detection of CYP3A5 polymorphism and tacrolimus neurotoxicity after renal transplantation.Methods A total number of 116 patients who received tacrolimus after renal transplantation in our hospital from 2017 to 2020 were analyzed retrospectively.Direct DNA sequencing was used to detect CYP3A5 polymorphism,and tacrolimus concentrations and neurotoxicity were observed in patients with different genes at different time points after surgery.Results The incidence of neurotoxicity in patients receiving tacrolimus after renal transplantation was 38%,and in 116 renal transplant patients,the plasma concentrations of tacrolimus in patients with CYP3A5*3/*3 genotype were lower than those with CYP3A5*1/*1 and CYP3A5*1/*3 genotypes within 2 weeks postoperatively,but higher than those with CYP3A5*1/*1 and CYP3A5*1/*3 genotypes at 2 weeks postoperatively and in the long term,there’s also a higher chance of neurotoxicity.Conclusion The concentration of tacrolimus in blood is an important factor of early neurological complications after renal transplantation.Patients with the CYP3A5*3/*3 genotype were metabolizing slowly and had a higher probability of neurotoxicity.Blood concentrations of tacrolimus in patients with the CYP3A5*3/*3 genotype were higher than the patients with other two genotypes with the same dose at two weeks after transplant,and the required dose should be reduced.