Clinical research

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

  • Qingqing DU ,
  • Zexin HOU ,
  • Jun LI ,
  • Ying HU ,
  • Guolei CAO ,
  • Siyuan LI
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  • 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
LI JUN, E-mail: xjlijun@163.com.

Received date: 2021-11-25

  Online published: 2022-05-09

Supported by

Science and Technology Project of Xinjiang Production and Construction Corps(2021AB031);Achievement Transformation and Technology Extension Project of Shihezi University(CGZH201911)

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.

Cite this article

Qingqing DU , Zexin HOU , Jun LI , Ying HU , Guolei CAO , Siyuan LI . Correlation between FRA-2 mRNA expression, DNA methylation level and metabolic syndrome[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(3) : 350 -356 . DOI: 10.3969/j.issn.1674-8115.2022.03.013

References

1 SAKLAYEN M G. The global epidemic of the metabolic syndrome[J]. Curr Hypertens Rep, 2018, 20(2): 12.
2 陈树春. 钠-葡萄糖共转运蛋白2抑制剂对代谢综合征的影响[J]. 中华老年心脑血管病杂志, 2021, 23(12): 1233-1235.
3 GREENBERG M V C, BOURC'HIS D. The diverse roles of DNA methylation in mammalian development and disease[J]. Nat Rev Mol Cell Biol, 2019, 20(10): 590-607.
4 SAMBLAS M, MILAGRO F I, MARTíNEZ A. DNA methylation markers in obesity, metabolic syndrome, and weight loss[J]. Epigenetics, 2019, 14(5): 421-444.
5 BIRNHUBER A, BIASIN V, SCHNOEGL D, et al. Transcription factor Fra-2 and its emerging role in matrix deposition, proliferation and inflammation in chronic lung diseases[J]. Cell Signal, 2019, 64: 109408.
6 DROSOS I, CHALIKIAS G, PAVLAKI M, et al. Differences between perivascular adipose tissue surrounding the heart and the internal mammary artery: possible role for the leptin-inflammation-fibrosis-hypoxia axis[J]. Clin Res Cardiol, 2016, 105(11): 887-900.
7 JIANG L, SU H R, WU X Y, et al. Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease[J]. Nat Commun, 2020, 11(1): 1517.
8 WRANN C D, EGUCHI J, BOZEC A, et al. FOSL2 promotes leptin gene expression in human and mouse adipocytes[J]. J Clin Invest, 2012, 122(3): 1010-1021.
9 PAN S, LI M Y, YU H B, et al. microRNA-143-3p contributes to inflammatory reactions by targeting FOSL2 in PBMCs from patients with autoimmune diabetes mellitus[J]. Acta Diabetol, 2021, 58(1): 63-72.
10 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021, 13(4): 315-409.
11 PEARCE M S, MCCONNELL J C, POTTER C, et al. Global LINE-1 DNA methylation is associated with blood glycaemic and lipid profiles[J]. Int J Epidemiol, 2012, 41(1): 210-217.
12 侯泽鑫, 李思源, 曹国磊, 等. 新疆维吾尔族代谢综合征患者血清FOS相关抗原2蛋白浓度变化及与危险因素个数的关系[J]. 医学研究生学报, 2021, 34(7): 717-720.
13 赵天明, 王增武, 张林峰, 等. 北方农村35岁及以上人群代谢综合征患病情况调查[J]. 中华疾病控制杂志, 2015, 19(5): 439-442, 446.
14 Chiurazzi M, Cozzolino M, Orsini R C, et al. Impact of genetic variations and epigenetic mechanisms on the risk of obesity[J]. Int J Mol Sci, 2020, 21(23): 9035.
15 LI J, LI S Y, HU Y, et al. The expression level of mRNA, protein, and DNA methylation status of FOSL2 of Uyghur in Xinjiang in type 2 diabetes[J]. J Diabetes Res, 2016, 2016: 5957404.
16 LIN J B, LIN S W, WU Y H, et al. Hypomethylation of the angiotensin Ⅱ type Ⅰ receptor (AGTR1) gene along with environmental factors increases the risk for rssential Hypertension[J]. Cardiology, 2017, 137(2): 126-135.
17 岳薇薇, 胡大春. 肾素-血管紧张素-醛固酮系统在高血压遗传病理机制中的研究进展[J]. 医学综述, 2018, 24(22): 4440-4444.
18 全贞玉, 姜允吉, 金海英, 等. 内脂素与代谢综合征及其组分的相关性[J]. 中国慢性病预防与控制, 2014, 22(5): 602-604.
19 XIE F F, DENG F Y, WU L F, et al. Multiple correlation analyses revealed complex relationship between DNA methylation and mRNA expression in human peripheral blood mononuclear cells[J]. Funct Integr Genomics, 2018, 18(1): 1-10.
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