Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant

• Published in: JACC. Basic to translational science 2024-09, Vol.9 (9), p.1073-1084
• Main Authors: 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.
• Format: Article
• Language: English
• Subjects: heart failure with preserved ejection fraction; intercellular adhesion molecule-1; Original Research - Clinical; proteomics; rs5491
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2024.05.016

[Display omitted] •The ICAM1 pK56M (rs5491) HFpEF risk variant is associated with several individual inflammatory proteins and an inflammatory protein network, which may identify immune pathways that drive HFpEF.•rs5491-specific protein networks are associated with derangements in several measures of cardiac structure and function that are commonly seen in HFpEF.•Patients with HFpEF have higher levels of rs5491-specific inflammatory proteins than do comorbidity-matched control patients. A common missense variant in ICAM1 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 ICAM1 pK56M (rs5491) variant.