天津医药

天津医药 ›› 2022, Vol. 50 ›› Issue (6): 633-638.doi: 10.11958/20212464

• 临床研究 • 上一篇    下一篇

MTHFR基因启动子甲基化与糖尿病肾病发病的关系研究

陈灵芝，钟开义，陈立国   

  1. 海南西部中心医院肾内科（邮编571700）
  • 收稿日期:2021-11-03 修回日期:2022-02-24 出版日期:2022-06-15 发布日期:2023-12-20
  • 通讯作者: 陈灵芝 E-mail:rsj214854@163.com

Study on the relationship between methylation of MTHFR promoter methylation and diabetic nephropathy

CHEN Lingzhi, ZHONG Kaiyi, CHEN Liguo   

  1. Department of Nephrology, Hainan West Central Hospital, Danzhou 571700, China
  • Received:2021-11-03 Revised:2022-02-24 Published:2022-06-15 Online:2023-12-20

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摘要： 摘要：目的　探讨亚甲基四氢叶酸还原酶（MTHFR）基因启动子甲基化与糖尿病肾病发病的关系。方法　根据慢性肾脏病分期标准将81例糖尿病肾病患者（肾病组）分为1~2期组（26例），3a~3b期组（39例），4~5期组（16例），另选择139例单纯2型糖尿病患者（单纯糖尿病组）和51例体检志愿者（对照组）。检测3组血清MTHFR基因启动子甲基化、三酰甘油（TG）、同型半胱氨酸（Hcy）、糖化血红蛋白（HbA1c）、尿微量白蛋白、肾小球滤过率估算值（eGFR）水平。比较组间上述指标的差异，Logistic回归和ROC曲线分析MTHFR基因启动子甲基化与2型糖尿病患者发生糖尿病肾病的关系。结果　与对照组比较，肾病组、单纯糖尿病组MTHFR基因启动子甲基化水平降低（P＜0.05）；与单纯糖尿病组比较，肾病组MTHFR基因启动子甲基化水平亦降低（P＜0.05）。1~2期、3a~3b期、4~5期组患者MTHFR基因启动子甲基化水平依次降低（P＜0.05）。多因素Logistic回归分析显示，高血压和尿微量白蛋白升高是2型糖尿病患者发生糖尿病肾病的危险因素，eGFR、MTHFR基因启动子甲基化水平升高是2型糖尿病患者发生糖尿病肾病的保护因素（P＜0.05）。与单独MTHFR基因启动子甲基化、尿微量白蛋白、eGFR相比，三指标并联检查的诊断效能较高，敏感度和特异度较好。结论　糖尿病患者血清MTHFR基因启动子甲基化水平降低，且与2型糖尿病患者发生糖尿病肾病以及疾病严重程度加重有关。

关键词: 糖尿病, 2型；糖尿病肾病；亚甲基四氢叶酸还原酶（NADPH）；DNA甲基化；尿微量白蛋白；肾小球滤过率估算值

Abstract: Abstract: Objective　To investigate the relationship between methylation of methylenetetrahydrofolate reductase (MTHFR) promoter and diabetic nephropathy. Methods　According to the staging criteria of chronic kidney disease, 81 patients with diabetic nephropathy (the nephropathy group) were divided into the stage 1-2 group (26 cases), the stage 3a-3b group (39 cases) and the stage 4-5 group (16 cases). Another 139 patients with simple type 2 diabetes were used as the simple diabetes group and 51 healthy volunteers were used as the control group. The serum levels of MTHFR promoter methylation, triacylglycerol (TG), homocysteine (Hcy), glycosylated hemoglobin (HbA1c), urinary microalbumin and estimated glomerular filtration rate (EGFR) were detected in the three groups. The differences in these indicators were compared between groups. Logistic regression and ROC curve were used to analyze the relationship between MTHFR gene promoter methylation and diabetic nephropathy in patients with type 2 diabetes mellitus. Results　Compared with the control group, the level of MTHFR promoter methylation was decreased in the nephropathy group and the simple diabetes group (P＜0.05). Compared with the simple diabetes group, the level of MTHFR promoter methylation was decreased in the nephropathy group (P＜0.05). The levels of MTHFR promoter methylation decreased successively in the stage 1 to 2 group, the stage 3a to 3b group and the stage 4-5 group (P＜0.05). Multivariate Logistic regression analysis showed that hypertension and high level of urinary microalbumin were risk factors of diabetic nephropathy in patients with type 2 diabetes, and the high level of eGFR and methylation of MTHFR gene were protective factors of diabetic nephropathy in type 2 diabetes (P＜0.05). Compared with methylation of MTHFR gene, urinary microalbumin and eGFR alone, the parallel examination of three indexes had a higher diagnostic efficiency, better sensitivity and specificity. Conclusion　The level of MTHFR promoter methylation in patients with diabetes is decreased, and it is associated with the occurrence of diabetic nephropathy and the aggravation of disease severity in type 2 diabetes patients.

Key words:  diabetes mellitus, type 2, diabetic nephropathies, methylenetetrahydrofolate reductase (NADPH2), DNA methylation, urine microalbumin, estimated glomerular filtration rate