FOXP3基因甲基化在2型糖尿病肾病中的作用  

DNA methylation of FOXP3 in the process of type 2 diabetic nephropathy

作　　者：李小峰[1] 廖静[2] LI Xiaofeng LIAO Jing(Longgang District People＇ s Hospital of Shenzhen, Shenzhen, Guangdong 518172, China)

机构地区：[1]深圳市龙岗区人民医院,广东深圳518172 [2]深圳市龙岗区疾病预防控制中心,广东深圳518172

出　　处：《中国热带医学》2017年第7期664-667,共4页China Tropical Medicine

基　　金：深圳市科技计划项目(No.JCYJ20150402164314696);深圳市卫生计生系统科研项目(No.201402126);深圳市龙岗区科技发展资金(No.YLWS20150513174008294;YLWS20150511114456591)

摘　　要：目的探讨FOXP3基因甲基化在2型糖尿病肾病发病过程中的作用。方法将90名研究对象分为正常对照组、单纯糖尿病组、糖尿病肾病组。采用亚硫酸氢盐测序法检测FOXP3基因启动子区(^+2071,^+2182)的甲基化水平,以流式细胞术检测CD4^+CD25^+FOXP3^+T细胞表达率。结果单纯糖尿病组和糖尿病肾病组FOXP3基因启动子区5个Cp G位点均呈现高甲基化(100%),而正常对照组第5个Cp G位点(^+2156)可见低甲基化(90%)。与正常对照组相比,其余两组CD4^+CD25^+T细胞表达率均下降,差异有统计学意义(P<0.05)。不同组别之间CD4^+CD25^+FOXP3^+T细胞表达率差异有统计学意义(P<0.01),糖尿病肾病组低于其余两组(P<0.05)。三组之间CD4^+CD25^+FOXP3^+T细胞表达呈现随病情加重而下降的趋势。年龄、糖化血红蛋白、空腹血糖、白细胞、糖尿病病程与CD4^+CD25^+FOXP3^+T细胞表达率之间呈现负相关(P<0.05)。结论 FOXP3基因启动子区高甲基化和CD4^+CD25^+FOXP3^+T细胞表达率下调可能与2型糖尿病肾病发病相关。Objective To investigate effect of DNA methylation of FOXP3 gene in the process of type 2 diabeticnephropathies.Methods A total of 90 subjects were selected to divide into three groups,such as the control group,thediabetes group,and the diabetic nephropathies group.Bisulfite sequencing and flow cytometry was carried out to determineDNA methylation in the promoter region（~＋2071,~＋2182） of FOXP3 and rate of CD4~＋CD25~＋FOXP3~＋Treg cells.Results Thediabetes group and the diabetic nephropathies group displayed a hypermethylated FOXP3 promoter（100%） in the five Cp Gsites,and in the fifth Cp G site（~＋2156） in contrast to the control group that was partially methylated（90%）.Compared with thecontrol group,rates of CD4~＋CD25~＋T cells in other groups were significantly decreased（P〈0.05）.There was a significantdifference in the rate of CD4~＋CD25~＋FOXP3~＋Treg cells in different groups（P〈0.01）,which was statistically lower in the diabeticnephropathies group than in other groups（P〈0.05）.A downward tendency was observed in the rate of CD4~＋CD25~＋FOXP3~＋Tregcells in different groups as the condition was worsen.There was negative correlations（P〈0.05） between the rate of CD4~＋CD25~＋FOXP3~＋Treg cells and age,glycosylated hemoglobin,fasting plasma glucose,leukocyte,the duration of diabetes.Conclusion This study implied that hypermethylation in the promoter of FOXP3 and the decrease in the rate of CD4~＋CD25~＋FOXP3~＋Tregcells might be correlated with the pathogenesis of type 2 diabetic nephropathies.

关 键 词：叉头转录因子 DNA甲基化 糖尿病 糖尿病肾病 

分 类 号：R587.1[医药卫生—内分泌]