上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (3): 350-356.doi: 10.3969/j.issn.1674-8115.2022.03.013

• 论著 · 临床研究 • 上一篇    下一篇

FRA-2 mRNA表达及DNA甲基化水平与代谢综合征的相关性研究

杜晴晴1(), 侯泽鑫1, 李军2(), 胡颖3, 曹国磊4, 李思源1   

  1. 1.石河子大学医学院,石河子 832002
    2.石河子大学医学院第一附属医院内分泌代谢科,石河子 832002
    3.新疆医科大学第四附属医院神志科,乌鲁木齐 830099
    4.新疆医科大学附属肿瘤医院呼吸神经内科,乌鲁木齐 830011
  • 收稿日期:2021-11-25 出版日期:2022-03-28 发布日期:2022-05-09
  • 通讯作者: 李军 E-mail:xjduqq@163.com;xjlijun@163.com
  • 作者简介:杜晴晴(1997—),女,硕士生;电子信箱:xjduqq@163.com
  • 基金资助:
    新疆生产建设兵团科技攻关计划(2021AB031);石河子大学成果转化与技术推广项目(CGZH201911)

Correlation between FRA-2 mRNA expression, DNA methylation level and metabolic syndrome

Qingqing DU1(), Zexin HOU1, Jun LI2(), Ying HU3, Guolei CAO4, Siyuan LI1   

  1. 1.Shihezi University School of Medicine, Shihezi 832002, China
    2.Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi 832002, China
    3.Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi 830099, China
    4.Department of Respiratory Neurology, Xinjiang Medical University Cancer Hospital, Urumqi 830011, China
  • Received:2021-11-25 Online:2022-03-28 Published:2022-05-09
  • Contact: Jun LI E-mail:xjduqq@163.com;xjlijun@163.com
  • Supported by:
    Science and Technology Project of Xinjiang Production and Construction Corps(2021AB031);Achievement Transformation and Technology Extension Project of Shihezi University(CGZH201911)

摘要:

目的·探讨Fos相关抗原-2(Fos-related antigen-2,FRA-2)mRNA表达水平及DNA甲基化水平与代谢综合征(metabolic syndrome,MS)的关系。方法·采用病例-对照研究方法,纳入2020年6月—2021年6月于石河子大学医学院第一附属医院内分泌代谢科就诊的有MS危险因素(肥胖、高血脂、高血压、高血糖)的患者160例,分为MS组(危险因素≥3项,n=80)和非MS组(危险因素1~2项,n=80);另选取同期健康体检者纳入对照组(危险因素0项,n=80)。收集并记录年龄、体质量指数(body mass index,BMI)、腰围(waist circumference,WC)、舒张压(diastolic blood pressure,DBP)、收缩压(systolic blood pressure,SBP)等一般资料,测定空腹血糖(fasting plasma glucose,FPG)、三酰甘油(triacylglycerol,TAG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、空腹胰岛素(fasting serum insulin,FINS)、胰岛素抵抗指数(homeostasis model assessment-insulin resistance,HOMA-IR)等临床生化指标,反转录-聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)检测FRA-2 mRNA表达水平,碱基特异性裂解和基质辅助激光解析电离时间飞行质谱仪(matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry,MALDI-TOF-MS)测定FRA-2 DNA甲基化水平。3组之间性别比较采用Kruskal-Wallis H检验,年龄比较采用方差分析,临床生化指标、FRA-2 mRNA表达水平、FRA-2 DNA甲基化水平比较采用协方差分析; Spearman法分析FRA-2 DNA CpG单元甲基化水平与MS相关临床生化指标之间、FRA-2 mRNA表达水平与FRA-2 DNA甲基化水平之间的相关关系;采用线性回归分析FRA-2 DNA甲基化水平与MS危险因素个数的关系。结果·与对照组及非MS组相比,MS组年龄、BMI、WC、DBP、SBP、FPG、TAG、TC、LDL-C、HOMA-IR上升(均P<0.05),HDL-C降低(P=0.000),FRA-2 mRNA表达水平下降(F=49.155,P=0.000)。与对照组相比,非MS组和MS组4个FRA-2 DNA CpG单元甲基化水平上升(均P<0.05);与非MS组相比,MS组5个FRA-2 DNA CpG单元甲基化水平上升(均P<0.05)。线性回归分析结果显示,MS危险因素个数与FRA-2 DNA甲基化水平呈正相关(β=0.012,P=0.000)。Spearman法分析结果显示,测定的10个FRA-2 DNA CpG单元中CpG 3、CpG 8、CpG 9.10、CpG 12.13.14、CpG 19与WC、SBP、DBP、FPG、TAG、HDL-C之间都存在相关性(均P<0.05);FRA-2 mRNA表达水平与FRA-2 DNA甲基化水平呈负相关(r=-0.607,P=0.000)。结论·FRA-2基因甲基化水平与MS的发生有一定的相关性,FRA-2 DNA甲基化水平增高从而下调mRNA表达可能在MS发生中发挥作用。

关键词: 代谢综合征, Fos相关抗原-2, 甲基化, 相关性

Abstract:

Objective·To investigate the relationship between Fos-related antigen-2 (FRA-2) mRNA, DNA methylation levels and metabolic syndrome (MS).

Methods·A case-control study was used to include 160 patients with MS risk factors (obesity, hyperlipidemia, hypertension and hyperglycemia) who were admitted to the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Shihezi University School of Medicine from June 2020 to June 2021. They were divided into MS group (number of MS risk factors ≥3, n=80) and non-MS group (number of MS risk factors 1?2, n=80). In addition, healthy subjects at the same period were included in the control group (0 risk factor, n=80). The age, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were collected and recorded; Fasting plasma glucose (FPG), triacylglycerol (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting serum insulin (FINS) and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. FRA-2 mRNA expression level was detected by reverse transcription-polymerase chain reaction (RT-PCR), and FRA-2 DNA methylation level was determined by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Kruskal-wallis H test was used for gender comparison, ANOVA was used for age comparison, and covariance analysis was used for comparison of clinical biochemical indicators, FRA-2 mRNA expression level and FRA-2 DNA methylation level. Spearman method was used to analyze the correlation between the methylation level of FRA-2 DNA CpG unit and MS-related clinical biochemical indexes, and between the expression level of FRA-2 mRNA and the methylation level of FRA-2 DNA. The relationship between FRA-2 DNA methylation level and the number of MS risk factors was analyzed by linear regression analysis.

Results·Compared with the control group and the non-MS group, the age, BMI, WC, DBP, SBP, FPG, TAG, TC, LDL-C and HOMA-IR in the MS group were increased (all P<0.05), while HDL-C was decreased (P=0.000); the expression of FRA-2 mRNA in the MS group was decreased (F=49.155, P=0.000). Compared with the control group, the methylation levels of four FRA-2 DNA CpG units in the non-MS group and the MS group were increased (all P<0.05). Compared with the non-MS group, the methylation levels of five FRA-2 DNA CpG units in the MS group were increased (all P<0.05). The results of linear regression analysis showed that the number of MS risk factors was positively correlated with the level of FRA-2 DNA methylation (β=0.012, P=0.000). Spearman method analysis results showed that among the 10 detected FRA-2 DNA CpG units, CpG 3, CpG 8, CpG 9.10, CpG 12.13.14 and CpG 19 were correlated with WC, SBP, DBP, FPG, TAG and HDL-C (all P<0.05). The mRNA expression level of FRA-2 was negatively correlated with the DNA methylation level of FRA-2 (r=-0.607, P=0.000).

Conclusion·There is a certain correlation between the methylation level of FRA-2 gene and the occurrence of MS. Increasing the methylation level of FRA-2 DNA and thus down-regulating the mRNA expression may play a role in the occurrence of MS.

Key words: metabolic syndrome (MS), Fos-related antigen-2 (FRA-2), methylation, correlation

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