核调节干扰在亚洲人群中先发并预测2型糖尿病的发展
Pritesh R Jain1, Hong Kiat Ng1, Darwin Tay1
1Population and Global Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
medRxiv : the preprint server for health sciences
|February 24, 2025
概括
研究人员确定了DNA甲基化标记,可以预测亚洲人群的2型糖尿病 (T2D) 风险. 这些标记物形成甲基化风险评分 (MRS),为早期糖尿病检测和预防策略提供了潜力.
科学领域:
- 遗传学和表观遗传学
- 代谢疾病 代谢疾病
- 人口健康 人口健康
背景情况:
- 2型糖尿病 (T2D) 是一个重大的全球健康挑战.
- 识别预测生物标志物和理解潜在的监管途径对于T2D预防至关重要.
- 以前的研究已经探索了遗传和生活方式因素,但表观遗传的贡献需要进一步的研究.
研究的目的:
- 发现新的DNA甲基化生物标志物,用于预测亚洲人群未来的2型糖尿病 (T2D).
- 阐明与T2D发展相关的调控途径和生物网络.
- 评估基于甲基化的T2D分层风险评分的临床实用性.
主要方法:
- 在5709名亚洲人的全血中进行了基于阵列的全表观基因组关联研究 (EWAS).
- 确定了与T2D风险相关的显著CpG (细胞因子甲基化位点).
- 开发并验证了基于数组和基于测序的甲基化风险评分 (MRS).
主要成果:
- 从314个基因位点中确定了323个哨兵CPG,这些基因位点可以预测未来的T2D.
- 发现这些CpG与免疫激活和代谢途径 (胰岛素信号传递,脂肪酸代谢,脂质运输) 有关.
- 开发了一种基于数组的MRS (RR:5.2) 和基于测序的MRS (RR:8.3),强烈预测T2D,增加遗传风险.
- 在亚洲族群中观察到MRS的显著变化,解释了人口水平T2D风险差异.
结论:
- 整个表观基因组的关联研究揭示了T2D发展之前的核调节障碍.
- DNA甲基化标记物,特别是基于测序的MRS,对T2D显示出强大的预测能力.
- 甲基化标记物有潜在的风险分层和个性化糖尿病预防策略,特别是在不同的亚洲人群中.
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