Giro Pedro, Filipp Mallory, Zhang Michael J, Moser Ethan D, Thorp Edward B, Dalal Prarthana J, Shah Ravi V, Ellinor Patrick T, Cunningham Jonathan W, Jurgens Sean J, Sinha Arjun, Rasmussen-Torvik Laura, Kizer Jorge, Taylor Kent D, Greenland Philip, Psaty Bruce M, Tracy Russell P, Chen Lin Yee, Shah Amil M, Yu Bing, Shah Sanjiv J, Patel Ravi B
Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
JACC Basic Transl Sci. 2024 Aug 14;9(9):1073-1084. doi: 10.1016/j.jacbts.2024.05.016. eCollection 2024 Sep.
A common missense variant in among African American individuals (rs5491; pK56M) has been associated with risk of heart failure with preserved ejection fraction (HFpEF), but the pathways that lead to HFpEF among those with this variant are not clear. In this analysis of 92 circulating proteins and their associated networks, we identified 7 circulating inflammatory proteins associated with rs5491 among >600 African American individuals. Using weighted coexpression network analysis, 3 protein networks were identified, one of which was associated with rs5491. This protein network was most highly represented by members of the tumor necrosis receptor superfamily. The rs5491 variant demonstrated an inflammatory proteomic profile in a separate cohort of African American individuals. This analysis identifies inflammatory pathways that may drive HFpEF among African American individuals with the pK56M (rs5491) variant.
非裔美国人中一种常见的错义变体（rs5491；pK56M）与射血分数保留的心力衰竭（HFpEF）风险相关，但在携带该变体的人群中导致HFpEF的途径尚不清楚。在这项对92种循环蛋白及其相关网络的分析中，我们在600多名非裔美国人中鉴定出7种与rs5491相关的循环炎症蛋白。使用加权共表达网络分析，鉴定出3个蛋白网络，其中一个与rs5491相关。该蛋白网络以肿瘤坏死因子受体超家族成员最为显著。rs5491变体在另一组非裔美国人中表现出炎症蛋白质组学特征。该分析确定了可能在携带pK56M（rs5491）变体的非裔美国人中驱动HFpEF的炎症途径。
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