在COVID-19中严重疾病的遗传机制
Erola Pairo-Castineira1,2, Sara Clohisey1, Lucija Klaric2
1Roslin Institute, University of Edinburgh, Edinburgh, UK.
Nature
|December 11, 2020
概括
危急的COVID-19患者的基因变异揭示了新的治疗目标. 参与抗病毒防御和炎症的关键基因表明2019年严重冠状病毒疾病的潜在药物重用.
科学领域:
- 遗传学
- 免疫学
- 危急护理医学
背景情况:
- 宿主介导的肺炎对危急的COVID-19患者的死亡率有很大影响.
- 识别宿主遗传因素对于了解疾病机制和开发新疗法至关重要.
研究的目的:
- 在重症COVID-19患者中进行全基因组关联研究 (GWAS),以确定与严重疾病相关的遗传变异.
- 通过分析已识别的遗传关联的功能影响来探索潜在的治疗点.
主要方法:
- 关键护理中的死亡遗传学 (GenOMICC) 研究分析了来自英国208个重症监护室的2,244名危急COVID-19患者.
- 发现并复制了全基因组显著的关联.
- 使用孟德尔随机化和全转录组关联研究来研究基因表达和疾病关联.
主要成果:
- 发现了四种全基因组显著关联:rs10735079 (OAS1/ 2/3集群),rs74956615 (TYK2附近),rs2109069 (DPP9) 和rs2236757 (IFNAR2).
- IFNAR2的低表达和TYK2的高表达与危及生命的COVID-19有关.
- 肺组织中CCR2的高表达与严重的COVID-19相关.
结论:
- 遗传发现强调了宿主抗病毒反应和炎症途径在严重的COVID-19中所起的作用.
- 已识别的基因和途径为重新使用现有药物提供了潜在的目标.
- 需要进行进一步的大规模随机临床试验来验证这些发现并指导临床实践的变化.
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