NFATC1基因多态性对肾移植患者慢性排斥反应发生率的影响

目的:探讨NFATC1基因多态性对钙调磷酸酶抑制药(CNI)治疗的肾移植患者慢性排斥反应发生率的影响,为慢性排斥反应寻找遗传标记物。方法:以233例使用CNI治疗的肾移植患者为研究对象。慢性排斥反应由肾穿刺病理检查确定。采用基质辅助激光解离飞行时间质谱方法对NFATC1基因25个单核苷酸多态性(SNP)位点进行基因分型。SNP对慢性排斥反应发生率的影响采用Kaplan-Meier生存分析和多因素Cox比例风险模型进行评估。结果:Kaplan-Meier生存分析发现NFATC1 rs12959273位点与慢性排斥反应的发生相关,AA/AG型患者慢性排斥反应的发生率高于GG型(P=0.001);rs6506775位点也对慢性排斥反应的发生有影响,TT/TC型患者慢性排斥反应的发生率高于CC型(P=0.001)。多因素Cox回归纳入混杂因素后,发现rs12959273 AA/AG型患者发生慢性排斥反应的风险仍然高于GG型[风险比(HR)=3.883,95%CI(1.794,8.405),P=0.001];rs6506775 TT/TC型患者慢性排斥反应的发生率高于CC型[HR=3.715,95%CI(1.696,8.139),P=0.001]。结论:NFATC1 rs12959273 A和rs6506775 T等位基因携带者慢性排斥反应的发生率高于非携带者。这两个位点可能成为预测肾移植患者慢性排斥反应的遗传标记物,为优化CNI给药和个体化给药提供依据,改善肾移植患者的长期结局。

Influence of NFATC1 Polymorphisms on the Incidence of Chronic Rejection in Renal Transplant Patients

Objective:To investigate the effect of NFATC1 gene polymorphisms on the incidence of chronic rejection in CNI-treated renal transplant patients,and to find genetic markers for chronic rejection.Methods:A total of 233 CNI-treated renal transplant recipients were included in this study.Chronic rejection was determined by renal biopsy.Twenty-five single nucleotide polymorphisms(SNPs)of NFATC1 gene were detected using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry method.The influence of SNPs on the incidence of chronic rejection was evaluated using Kaplan-Meier survival analysis and multivariate Cox regression.Results:Kaplan-Meier analysis found that NFATC1 rs12959273 polymorphism was associated with chronic rejection,and the rate of chronic rejection was higher in patients with AA/AG than in those with the GG genotype(P=0.001);rs6506775 also had an impact on the rate of chronic rejection,patients with TT/TC took a greater risk than CC(P=0.001).The results of multivariate Cox regression were consistent with the Kaplan-Meier analysis.Patients with rs12959273 AA/AG took a hagher risk of chronic rejection than those with the GG genotype(HR=3.883,95%CI 1.794 to 8.405,P=0.001),and patients with rs6506775 TT/TC took a greater risk than CC(HR=3.715,95%CI 1.696 to 8.139,P=0.001).Conclusion:The incidence of chronic rejection is higher in NFATC1 rs12959273 A and rs6506775 T carriers than in non-carriers.These SNPs may be used as a genetic marker to predict the chronic rejection for renal transplant patients,lay the foundation for optimizing CNIs administration,and improve the long-term outcome of renal transplant patients.