慢性鼻炎组织的全基因组表观遗传学研究揭示了受调节的炎症,免疫和重塑途径
Tripti Brar1, Saurabh Baheti2, Michael J Marino1
1Department of Otolaryngology-Head & Neck Surgery, Mayo Clinic, Phoenix, AZ, USA.
American journal of rhinology & allergy
|August 16, 2023
概括
在DNA甲基化中的表观遗传变化与慢性鼻炎 (CRS) 有关. 这项研究在CRS患者中确定了明显的甲基化模式,这表明环境因素影响了这些表观遗传变化.
科学领域:
- 表观遗传学和分子生物学
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
- 免疫学 免疫学 免疫学
背景情况:
- 表观遗传学涉及诸如DNA甲基化等修改,这些修改会改变基因活性,而不会改变DNA序列.
- 可逆表观遗传变化具有治疗潜力,有七种表观遗传药物已批准用于癌症治疗.
- 在美国,之前没有研究过慢性鼻炎 (CRS) 的表观遗传学.
研究的目的:
- 为了研究与健康对照组相比,CRS患者的鼻腔DNA甲基化模式.
- 为了确定可能影响CRS患者的环境诱导的表观遗传变化.
主要方法:
- 减少表示双硫酸盐测序 (RRBS) 用于分析乙状 (CRS) 和低轮状 (控制) 粘膜组织中的DNA甲基化.
- 在RADMeth®生物统计包中,在CRS和对照组之间确定了差异甲基化区域 (DMR).
- 在DMR上进行了Ingenuity Pathway Analysis (IPA) 分析,以确定上游调节器和正规路径.
主要成果:
- 分析包括来自64名CRS患者的93个样本 (36名CRSwNP,28名CRSsNP) 和29名对照.
- 在CRS和对照样本之间,在13,662个CpG位点和1381个DMR中观察到显著差异.
- 确定的主要上游调节者包括TGFB1,TNF,TP53,DGCR8,β-雌激醇 (CRS与对照组);TGFB1,CTNNB1,脂多糖,ID2,TCF7L2 (CRSwNP与对照组);以及MYOD1,乙,ID2,ST8SIA4,LEPR (CRSsNP与对照组).
结论:
- 与对照组相比,在CRS,CRSwNP和CRSsNP患者中发现了不同的DNA甲基化模式.
- 这些潜在的环境诱导的表观遗传变化与炎症,免疫和重塑途径有关.
- 这些发现表明,在CRS中对上皮质完整性,细胞增殖,恒常性,血管透性和其他未表征的途径产生影响.
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