Methylation of the telomerase gene promoter region in umbilical cord blood of patients with gestational diabetes mellitus is associated with decreased telomerase expression levels and shortened telomere length.

IF 3.9 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Frontiers in Endocrinology Pub Date : 2025-03-11 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1502329
Shuhua Liu, Liping Xu, Yan Cheng, Dehong Liu, Bin Zhang, Xianxia Chen, Mingming Zheng
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Abstract

Objective: This study speculates that gestational diabetes mellitus (GDM) may reduce fetal telomere length (TL),which may be related to modification of methylation in the promoter region of the telomerase (TE) gene promoter region.

Methods: In this study, umbilical cord blood samples from patients with and without GDM (N = 100 each) were analyzed by prospective case-control. The TL, TE expression levels, and methylation levels of TERT and TERC gene promoter regions in two groups were measured. The significance of the methylation level of each CpG locus employed logistic regression analysis of R software, and the analysis of covariance (ANCOVA) was used to control the influence of confounding factors. Correlation analysis was performed by the Spearman.

Results: The TL and TE expression levels of the offspring of GDM patients were decreased despite adjusting for PBMI, PWG, and TG. A total of two CpG islands were screened in the promoter region of the TERT gene and three fragments (TERT_2, TERT_3, and TERT_4) containing a total of 70 CpG sites were designed. Additionally, four CpG sites of the TERT gene in the GDM group (TERT_2_40, TERT_2_47, TERT_3_46, and TERT_3_212) showed increased methylation levels compared with the control group (all P < 0.05). In the promoter region of the TERC gene, one CpG island containing 19 CpG loci was screened and designed, and the methylation levels of the two CpG sites were significantly different in TERC_1_67 (0.65 ± 0.21 versus 0.57 ± 0.30; P = 0.040) and TERC_1_120 (0.68 ± 0.23 versus 0.59 ± 0.27; P = 0.014). The methylation levels of TERC gene fragments of GDM patients were significantly higher than those of the control group (0.69 ± 0.06 versus 0.65 ± 0.08, P = 0.001).

Conclusion: This study revealed that GDM may induce decreased TE expression by increasing the methylation levels of TE genes promoter region, thereby reducing the TL.

妊娠期糖尿病患者脐带血端粒酶基因启动子区甲基化与端粒酶表达水平降低和端粒长度缩短有关。
目的:本研究推测妊娠期糖尿病(GDM)可能导致胎儿端粒长度(TL)减少,这可能与端粒酶(TE)基因启动子区域甲基化修饰有关。方法:采用前瞻性病例对照的方法,对GDM患者和非GDM患者的脐带血样本(N = 100)进行分析。检测两组患者的TL、TE表达水平及TERT、TERC基因启动子区甲基化水平。各CpG位点甲基化水平的显著性采用R软件进行logistic回归分析,协方差分析(ANCOVA)控制混杂因素的影响。采用Spearman进行相关分析。结果:GDM患者后代在调整PBMI、PWG和TG后,TL和TE的表达水平均有所下降。在TERT基因启动子区域共筛选到两个CpG岛,设计了包含70个CpG位点的三个片段(TERT_2、TERT_3和TERT_4)。此外,与对照组相比,GDM组TERT基因的四个CpG位点(TERT_2_40、TERT_2_47、TERT_3_46和TERT_3_212)的甲基化水平升高(均P < 0.05)。在TERC基因启动子区,筛选设计了一个包含19个CpG位点的CpG岛,两个CpG位点的TERC_1_67甲基化水平差异显著(0.65±0.21 vs 0.57±0.30;P = 0.040)和TERC_1_120(0.68±0.23 vs 0.59±0.27;P = 0.014)。GDM患者TERC基因片段甲基化水平显著高于对照组(0.69±0.06 vs 0.65±0.08,P = 0.001)。结论:本研究揭示GDM可能通过增加TE基因启动子区甲基化水平,从而降低TE表达,从而降低TL。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Frontiers in Endocrinology
Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
5.70
自引率
9.60%
发文量
3023
审稿时长
14 weeks
期刊介绍: Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.
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