介质素-1受体对手基因 (IL1RN) 变体调节COVID-19的细胞因子释放综合征和死亡率
Mukundan Attur1, Christopher Petrilli2, Samrachana Adhikari3
1Division of Rheumatology, Department of Medicine, New York University Langone Orthopedic Hospital, New York University Langone Health, New York, New York, USA.
The Journal of infectious diseases
|June 13, 2024
概括
在IL1RN基因中单核酸变异,特别是CTA单核型和rs419598 C/C变异,与严重COVID-19的男性减少炎症和降低死亡率有关.
科学领域:
- 免疫遗传学 免疫遗传学
- 病毒病原体的产生
- 基因组医学是基因组医学.
背景情况:
- 严重急性呼吸系统综合征冠状病毒2 (SARS-CoV-2) 感染可能导致细胞因子释放综合征 (CRS),一种超炎症状态.
- 由IL1RN编码的互白素1受体对手 (IL-1Ra) 在调节炎症反应中起着至关重要的作用.
- 在IL1RN中的遗传变异可能会影响SARS-CoV-2感染中的个体易感性和疾病严重程度.
研究的目的:
- 调查IL1RN基因的单核酸变体 (SNV) 和单核酸类型之间的关联,以及SARS-CoV-2感染患者中CRS和死亡率的发展.
- 探索IL1RN遗传变异在调节宿主对SARS-CoV-2的炎症反应中的潜在作用.
主要方法:
- 在一组2589名住院的SARS-CoV-2患者中,对IL1RN单核酸变异 (SNV) 和单核酸变异的基因定型,包括rs419598,rs315952和rs9005.
- 分析IL1RN遗传标记物,炎症的实验室标记物和患者死亡率之间的关联.
- 按性别和年龄分层分析,以确定具有差异反应的特定人口群体.
主要成果:
- 与女性 (13.1%) 相比,男性 (17.3%) 的死亡率更高.
- 携带IL1RN CTA单元型的携带者显示炎症标志物减少,IL-1Ra水平增加.
- rs419598 C/C基因型与明显减少的炎症生物标志物和数量较低的男性死亡率有关,特别是那些年龄小于74岁的人 (80%的减少).
结论:
- IL1RN CTA 哈普洛型和rs419598 C/C 变体与SARS-CoV-2 感染的男性患者的CRS减弱和死亡率降低有关.
- 这些发现表明,IL1RN遗传途径通过内源性抗炎机制调节COVID-19的严重程度.
- 准IL1RN途径可能是一个潜在的治疗策略,用于在特定患者群体中管理严重的COVID-19.
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