Department of Endocrinology, The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No.1 DaHua Road, Dong Dan, Beijing, 100730, People's Republic of China.
The Savaid School of Medicine, University of Chinese Academy of Sciences, Beijing, People's Republic of China.
Clin Epigenetics. 2021 Jun 6;13(1):123. doi: 10.1186/s13148-021-01109-2.
Type 2 diabetes mellitus (T2DM) and hypothyroidism are two common endocrine diseases and the phenomenon that the prevalence of diabetes-related hypothyroidism shows a significant upward trend deserves further attention, but the specific pathogenesis is not yet clear. The study aimed to explore the molecular mechanisms on DNA methylation regulating gene expression and participating in diabetes-related hypothyroidism through genome-wide DNA methylation and RNA sequencing.
The prevalence of hypothyroidism in T2DM patients was significantly higher than that in patients without T2DM (P = 0.018). Meanwhile, high TSH and low T3 and T4 levels were detected in diabetic mice. Low T3 and T4 levels were detected in Nthy-ori3-1 cells incubated in high-glucose medium. Differentially expressed genes (DEGs) and differentially methylated regions (DMRs) were detected by RNA sequencing and reduced representation bisulfite sequencing in Nthy-ori3-1 cells cultured in high-glucose and normal medium. Functional enrichment analyses reveled that DMRs and DEGs were related to significant pathways including Ras, Wnt and MAPK pathways.
We observed the potential connection between T2DM and hypothyroidism. This study was the first one carrying out DNA methylation and gene expression profiles to explore epigenetic modification in diabetes-related hypothyroidism, which provided information for the detailed study of the molecular mechanism in diabetes-related hypothyroidism.
2 型糖尿病（T2DM）和甲状腺功能减退症是两种常见的内分泌疾病，糖尿病相关甲状腺功能减退症的患病率呈显著上升趋势，值得进一步关注，但具体发病机制尚不清楚。本研究旨在通过全基因组 DNA 甲基化和 RNA 测序，探讨 DNA 甲基化调节基因表达并参与糖尿病相关甲状腺功能减退症的分子机制。
T2DM 患者甲状腺功能减退症的患病率明显高于非 T2DM 患者（P=0.018）。同时，糖尿病小鼠中检测到高 TSH 和低 T3、T4 水平。在高糖培养基中孵育的 Nthy-ori3-1 细胞中检测到低 T3 和 T4 水平。在高糖和正常培养基中培养的 Nthy-ori3-1 细胞中，通过 RNA 测序和简化代表性双硫代嘧啶测序检测到差异表达基因（DEGs）和差异甲基化区域（DMRs）。功能富集分析表明，DMRs 和 DEGs 与 Ras、Wnt 和 MAPK 等重要途径有关。
我们观察到 T2DM 和甲状腺功能减退症之间存在潜在联系。本研究首次进行 DNA 甲基化和基因表达谱分析，探讨了糖尿病相关甲状腺功能减退症中的表观遗传修饰，为糖尿病相关甲状腺功能减退症的分子机制的详细研究提供了信息。
