在小岛自身免疫开始时,DNA甲基化的纵向变化区分了小岛自身免疫的逆转与进展
Patrick M Carry1,2,3, Lauren A Vanderlinden2, Randi K Johnson2,3
1Colorado Program for Musculoskeletal Research, Department of Orthopedics, University of Colorado, Aurora, CO, United States.
Frontiers in immunology
|June 25, 2024
概括
在1型糖尿病 (T1D) 岛屿自身免疫 (IA) 进展期间的DNA甲基化 (DNAm) 变化因疾病结果而异. 这些DNAm差异与免疫和β细胞功能有关,为T1D发展提供了洞察力.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 1型糖尿病 (T1D) 的发展包括一个临床前阶段,称为小岛自身免疫 (IA).
- IA是异质的,个体表现出不同的自身抗体轨迹.
- 了解IA期间的DNA甲基化 (DNAm) 变化对于预测T1D进展至关重要.
研究的目的:
- 确定小岛自身抗体血清转换 (SV) 前后DNAm变化的差异.
- 为了比较这些DNAm在三个不同的IA进展表型中的变化:逆转者,维护者和T1D的进展者.
- 为了研究与这些DNAm变化相关的基因组区域.
主要方法:
- 一项全表观基因组关联研究 (EWAS) 使用来自年轻人糖尿病自身免疫研究 (DAISY) 队列的纵向DNAm数据.
- 在被归类为回归者 (n=41),维持者 (n=60) 或进展者 (n=42) 的参与者中,在SV前和SV后的访问之间比较DNAm.
- 使用线性混合模型进行统计分析,并根据细胞比例,年龄和性别进行调整.
主要成果:
- 在三个组中,DNAm的变化在一个特定的部位和11个基因组区域不同.
- 平均DNAm水平 (SV前和后) 在组之间在22个基因组区域之间有所不同.
- 在SV前访问的中位数年龄较年轻的进步者 (2.2岁) 与逆转者 (6.0岁) 和维持者 (5.7岁) 相比.
结论:
- 在与β细胞功能和免疫细胞分化/功能相关的区域中,确定了差异变化的DNAm区域.
- 这些发现突显了表观遗传修饰在IA进展的多样化途径中的作用.
- 这项研究提供了对T1D发展背后的分子机制和疾病轨迹的潜在生物标志物的洞察.
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