鉴定CD209作为COVID-19感染后2型糖尿病的干预靶点：来自蛋白质组全孟德尔随机化的见解

Diabetes Pub Date : 2025-04-01 DOI:10.2337/db24-0677

Jiaying Zhang, Feng Jiao, Zhenqian Wang, Chenfeng Zou, Xiangjun Du, Dewei Ye, Guozhi Jiang

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引用次数: 0

摘要

越来越多的证据表明，与未感染的人相比，感染2019冠状病毒病（COVID-19）的人患2型糖尿病（T2D）的风险更高。然而，这种关系背后的机制仍然知之甚少。在这项研究中，我们旨在通过蛋白质组范围的孟德尔随机化（MR）分析，系统评估3283种血浆蛋白在COVID-19易感性与T2D之间的关联中的介导作用。通过反向MR、独立数据集验证和共定位分析来验证MR结果的鲁棒性。进一步进行中介分析，量化中介效应。进行了蛋白质和t2d相关表型之间的MR分析，以增强对潜在机制的理解。最后，对鉴定的蛋白进行了药物性评价。四种与COVID-19易感性相关的蛋白（ABO、CD209、CUZD1和QXOS2）与T2D有显著的因果关系。CD209蛋白在验证和共定位分析中表现出显著的相关性，被确定为因果介导蛋白。中介分析显示，CD209显著介导了COVID-19对T2D易感性的总效应（β间接[95%CI]: 0.083[0.014-0.152]， P=0.019）。进一步的磁共振分析显示CD209与糖化血红蛋白、空腹血糖、空腹胰岛素和腰臀比之间存在显著关联。药物性评价表明，CD209可与α - d -甘露糖结合，并与包括二肽基肽酶4 （DPP4）在内的9个T2D药物靶点相互作用。我们的研究结果表明，CD209可能是COVID-19感染个体预防T2D的潜在干预靶点，为COVID-19和T2D之间的病理生理学联系提供了新的见解。

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Identification of CD209 as an Intervention Target for Type 2 Diabetes After COVID-19 Infection: Insights From Proteome-Wide Mendelian Randomization.

Article highlights: Increasing evidence links coronavirus disease 2019 (COVID-19) infection with heightened type 2 diabetes (T2D) risk; however, the mechanisms underlying this relationship remain poorly understood. We aimed to identify mediating proteins linking COVID-19 infection with T2D, elucidating how COVID-19 might heighten T2D risk. Protein CD209 and central obesity potentially play a crucial role between COVID-19 susceptibility and T2D. Our results highlight CD209 as a potential intervention target for T2D prevention following COVID-19 infection.

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Diabetes

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