Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant

Pedro Giro; Mallory Filipp; Michael J Zhang; Ethan D Moser; Edward B Thorp; Prarthana J Dalal; Ravi V Shah; Patrick T Ellinor; Jonathan W Cunningham; Sean J Jurgens; Arjun Sinha; Laura Rasmussen-Torvik; Jorge Kizer; Kent D Taylor; Philip Greenland; Bruce M Psaty; Russell P Tracy; Lin Yee Chen; Amil M Shah; Bing Yu; Sanjiv J Shah; Ravi B Patel

doi:10.1016/j.jacbts.2024.05.016

Proteomic Profile of the ICAM1 p.K56M HFpEF Risk Variant

JACC Basic Transl Sci. 2024 Aug 14;9(9):1073-1084. doi: 10.1016/j.jacbts.2024.05.016. eCollection 2024 Sep.

Authors

Pedro Giro¹, Mallory Filipp², Michael J Zhang³, Ethan D Moser³, Edward B Thorp², Prarthana J Dalal¹, Ravi V Shah⁴, Patrick T Ellinor^{5

6

7}, Jonathan W Cunningham^{5

8}, Sean J Jurgens^{5

6

9}, Arjun Sinha¹, Laura Rasmussen-Torvik¹⁰, Jorge Kizer¹¹, Kent D Taylor¹², Philip Greenland¹⁰, Bruce M Psaty¹³, Russell P Tracy¹⁴, Lin Yee Chen³, Amil M Shah¹⁵, Bing Yu¹⁶, Sanjiv J Shah¹, Ravi B Patel^{1

10}

Affiliations

¹ Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
² Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
³ Division of Cardiology, University of Minnesota Medical Center, Minneapolis, Minnesota, USA.
⁴ Division of Cardiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁵ Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
⁶ Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Demoulas Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁸ Division of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
⁹ Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Heart Failure and Arrhythmias, Amsterdam UMC location, University of Amsterdam, Amsterdam, the Netherlands.
¹⁰ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹¹ Division of Cardiology, University of California-San Francisco, San Francisco, California, USA.
¹² The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
¹³ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Systems and Population Health, University of Washington, Seattle, Washington, USA.
¹⁴ Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, USA.
¹⁵ Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
¹⁶ Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center, Houston, Texas, USA.

Abstract

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.

Keywords: heart failure with preserved ejection fraction; intercellular adhesion molecule-1; proteomics; rs5491.

Grants and funding

R01 HL167986/HL/NHLBI NIH HHS/United States