FOXP3基因启动子区甲基化与肾移植术后Th1/Th2水平和排斥反应的相关性分析

Analysis of the correlation between FOXP3 gene promoter methylation and Th1/Th2 level and rejection reaction after renal transplantation

目的:分析FOXP3基因启动子区甲基化与肾移植术后Th1/Th2水平及排斥反应的相关性。方法:将2010年至2019年12月于新疆医科大学第一附属医院行肾脏移植治疗的120例患者纳入研究,根据患者术后3个月是否出现急性排斥反应(AR)将其分为AR组及Non-AR组,比较两组患者基线临床资料,辅助性T细胞1(Th1)、Th2、Th/Th2及FOXP3基因启动子区甲基化水平,采用多因素Logistic回归模型对影响AR的因素进行分析,并采用Pearson相关性模型分析FOXP3基因启动子区甲基化水平与Th1/Th2水平的相关性。结果:AR组患者Th1、Th1/Th2及FOXP3基因启动子区甲基化水平明显高于Non-AR组(t=2.888,2.055,2.984,均P<0.05),Th2及FOXP3蛋白水平明显低于Non-AR组(t=2.665,2.155,均P<0.05);多因素Logistics回归分析示高Th1及FOXP3基因启动子区甲基化水平是AR的独立危险因素(OR=1.390,1355.480,均P<0.05),而高Th2水平是AR的保护因素(OR=0.560,P=0.001);相关性分析显示,FOXP3基因启动子区甲基化水平与FOXP3蛋白呈负相关关系(r=-0.879,P<0.001),与Th1/Th2水平呈正相关关系(r=0.810,P<0.001),而FOXP3蛋白与Th1/Th2水平呈负相关关系(r=-0.881,P<0.001)。结论:FOXP3基因启动子区甲基化水平升高后,FOXP3基因蛋白表达水平降低,影响患者体内Th1/Th2细胞表达,从而使患者体内免疫状态发生变化,进而可能诱发排斥反应。

Objective:To analyze the correlation between FOXP3 gene promoter methylation and Th1/Th2 level and rejection reaction after renal transplantation.Methods:A total of 120 patients who underwent renal transplantation in ourhospital from Dec.2010 to Dec.2019 were divided into acute rejection(AR)group and Non-AR group according to whether they had acute rejection 3 months after operation.The baseline clinical data and promoter methylation levels of helper T cell 1(Th1),Th2,Th/Th2 and FOXP3 genes were compared between the two groups.Multivariate Logistic regression was used to analyze the factors affecting AR.Pearson correlation analysis was used to analyze the correlation between FOXP3 gene promoter methylation level and Th1/Th2 level.Results:The methylation level of Th1,Th1/Th2 and FOXP3 gene promoter in AR group was significantly higher than that in Non-AR group(t=2.888,2.055,2.984,all P<0.05),while the protein levels of Th2 and FOXP3 were significantly lower than those in Non-AR group(t=2.665,2.155,all P<0.05).Multivariate Logistics regression analysis showed that high Th1 and methylation level in the promoter region of FOXP3 gene were independent risk factors for AR(OR=1.390,1355.480,all P<0.05),while high Th2 level was a protective factor for AR(OR=0.560,P=0.001).Correlation analysis showed that the methylation level in the promoter region of FOXP3 gene was negatively correlated with FOXP3 protein(r=-0.879,P<0.001),and positively correlated with Th1/Th2(r=0.810,P<0.001),while FOXP3 protein was negatively correlated with Th1/Th2(r=-0.881,P<0.001).Conclusion:After the methylation level of FOXP3 gene promoter increases,the expression level of FOXP3 gene protein decreases,which affects the expression of Th1/Th2 cells in patients,which changes the immune status of patients and may induce rejection reaction.