在HIV感染者中,与先前的结核病感染相关的DNA甲基化模式
Joseph Baruch Baluku1,2, Sharon Namiiro3,4, Daphine Kigongo Zawedde5
1Makerere University Lung Institute, PO Box 26343, Kampala, Uganda. bbjoe18@gmail.com.
Scientific reports
|August 19, 2025
概括
在艾滋病毒感染者 (PWH) 之前的结核病 (TB) 感染加快了表观遗传衰老,并改变了DNA甲基化模式. 这些变化与神经系统疾病,心血管疾病和各种癌症的风险增加有关.
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
- 传染性疾病 传染性疾病
背景情况:
- 以前的结核病 (TB) 感染与长期的健康风险有关,包括癌症,心血管和神经疾病,特别是在艾滋病毒感染者 (PWH) 中.
- 潜在的机制,特别是像DNA甲基化 (DNAm) 这样的表观遗传修饰,在这个人群中仍然不太了解.
研究的目的:
- 为了调查DNA甲基化模式和相关的生物途径在PWH与或没有先前的结核病感染.
- 评估表观遗传年龄加速及其与PWH先前结核病状况的关联.
主要方法:
- 使用Illumina MethylationEPIC BeadChip在30个PWH的血液样本中进行DNAm分析 (根据先前的潜在结核病感染,治疗的活跃结核病或没有结核病进行分类).
- 估计表观遗传年龄和计算年龄加速.
- 差异甲基化CpG (dmCpG) 和区域 (DMR) 的识别.
- 功能性丰富分析 (基因本体学,KEGG,PANTHER,DisGeNET,dbGaP) 进行,错误发现率 (FDR) <0.05.
主要成果:
- PWH表现出显著的表观遗传年龄加速 (平均19.32年>时间年龄),在那些以前患有结核病的人中更为明显 (21.60年).
- 当将以前的活跃结核病或潜伏结核病感染 (LTBI) 与没有结核病组进行比较时,确定了显著的dmCpG和DMR.
- 途径分析显示了神经发生,神经元分化,轴突引导,血小板激活,血管肌肉收缩和与癌症相关的途径 (例如,癌症中的蛋白质糖,肺癌,前列腺癌,乳腺癌,肝癌,甲状腺癌) 的丰富.
结论:
- 在PWH之前的结核病感染与明显的DNAm变化有关,这些变化会影响神经功能,心血管健康和癌症风险.
- 以前的结核病感染与更大的表观遗传年龄加速相关,这表明表观遗传机制在PWH的长期结核病相关并发症中发挥了作用.
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