Promoter Hypomethylation of miR-124 Gene Is Associated With Major Depressive Disorder

Duan Zeng; Shen He; Nan Zhao; Manji Hu; Jie Gao; Yimin Yu; Jingjing Huang; Yifeng Shen; Huafang Li

doi:10.3389/fnmol.2021.771103

Promoter Hypomethylation of miR-124 Gene Is Associated With Major Depressive Disorder

Front Mol Neurosci. 2021 Dec 21:14:771103. doi: 10.3389/fnmol.2021.771103. eCollection 2021.

Authors

Duan Zeng¹, Shen He¹, Nan Zhao², Manji Hu², Jie Gao³, Yimin Yu^{1

4}, Jingjing Huang^{1

4}, Yifeng Shen^{1

4}, Huafang Li^{1

4

5}

Affiliations

¹ Department of Psychiatry, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Psychiatry, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, China.
³ Yingbo Community Health Service Center, Shanghai, China.
⁴ Shanghai Clinical Research Center for Mental Health, Shanghai, China.
⁵ Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Abstract

Based on our previous studies and other evidence, miR-124 is an important biomarker and therapeutic target for major depressive disorder (MDD). The aim of this study was to clarify the role of miR-124 methylation in MDD and antidepressant effects from the perspective of epigenetics. MethylTarget™ was used to detect methylation levels of the three miR-124 precursor genes (MIR124-1, MIR124-2, and MIR124-3) in 33 pre- and post-treatment MDD patients and 33 healthy controls. A total of 11 cytosine-phosphate-guanine (CpG) islands in the three miR-124 precursor genes, including 222 CpG sites, were detected. All CpG islands were hypomethylated in MDD patients when compared to healthy controls and seven CpG regions were still identified with a statistically significant difference after Bonferroni correction. In addition, 137 of 222 CpG sites were found a statistical difference between MDD patients and controls, and 40 CpG sites were still statistically significant after Bonferroni correction. After performing the LASSO regression model, seven biomarkers with differential methylation among 40 CpG sites were identified. Mean methylation score was lower in MDD patients (z = -5.84, p = 5.16E-9). The AUC value reached 0.917 (95% CI: 0.854-0.981) to discriminate MDD and controls. No changes in methylation of the three miR-124 precursor genes were found in MDD patients following antidepressant treatment. The methylation of miR-124 could be a promising diagnostic biomarker for MDD.

Keywords: antidepressant; biomarker; major depressive disorder; methylation; miR-124.