与亚托匹性皮肤炎相关的基因变异调节LOC100294145表达,涉及interleukin-27的产生和1型干扰素信号传递
Wei Yi Teo1, Yi Ying Eliza Lim1, Yang Yie Sio1
1Department of Biological Sciences, National University of Singapore, Singapore.
The World Allergy Organization journal
|February 1, 2024
概括
在6p21.32位点的遗传变异通过提高LOC100294145表达增加了亚托皮炎 (AD) 风险. 这项研究揭示了一种涉及1型干扰素和AD中IL-27信号失调的发病模式.
科学领域:
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 亚托邦性皮肤炎 (AD) 是一种复杂的炎症性皮肤疾病,具有重要的遗传基础.
- 全基因组关联研究 (GWAS) 识别了与AD相关的遗传变异,但往往缺乏功能性见解.
- 需要采用多omics方法来理解AD相关的遗传变异的功能相关性.
研究的目的:
- 在6p21.32位点的AD相关遗传变异的特征.
- 阐明AD病变的潜在功能机制.
- 通过多主题战略调查LOC100294145在AD中的作用.
主要方法:
- 全基因组关联研究 (GWAS) 在6p21.32.32确定了与AD相关的变异.
- 在外周血液单核细胞 (PBMC) 中对LOC100294145进行基因型和表达分析.
- 在体外双露西法酶测定,共同表达分析,基因丰富 (g:Profiler) 和孟德尔随机化.
主要成果:
- 在6p21.32的特定基因变异 (rs116160149,rs115388857) 与AD风险增加和更高的LOC100294145表达有关.
- 在AD患者中,LOC100294145的表达显著升高.
- 实验室研究证实了基因型对LOC100294145促进体活性的影响;门德尔随机化支持其在IL-27和1型干扰素信号传递中的调节作用.
结论:
- 在6p21.32的遗传变异通过上调LOC100294145表达来赋予AD易感性.
- 一种多omics方法阐明了一种AD发病模式,涉及1型干扰素和IL-27信号通路中的失调的枢纽基因.
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