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Missense Genetic Variation of ICAM1 and Incident Heart Failure

Journal of Cardiac Failure, ISSN: 1071-9164, Vol: 29, Issue: 8, Page: 1163-1172
2023
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Researchers from Northwestern University Describe Findings in Heart Failure (Missense Genetic Variation of Icam1 and Incident Heart Failure)

2023 OCT 05 (NewsRx) -- By a News Reporter-Staff News Editor at Disease Prevention Daily -- New research on Heart Disorders and Diseases - Heart

Article Description

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF. We identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in the Atherosclerosis Risk in Communities (ARIC) study. Of the 3 missense variants, rs5491 was common in Black participants (minor allele frequency [MAF] > 20%) and rare in other race/ethnic groups (MAF < 5%). In Black participants, the presence of rs5491 was associated with higher levels of circulating ICAM-1 at 2 timepoints separated by 8 years. Among Black participants in MESA (n = 1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HR = 2.30; [95% CI 1.25–4.21; P  = 0.007]). The other ICAM1 missense variants (rs5498 and rs1799969) were associated with ICAM-1 levels, but there were no associations with HF. In ARIC, rs5491 was significantly associated with incident HF (HR = 1.24 [95% CI 1.02 – 1.51]; P  = 0.03), with a similar direction of effect for HFpEF that was not statistically significant. A common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.

Bibliographic Details

PEDRO Giro; DONALD M. LLOYD-JONES; SANJIV J. SHAH; RAVI B. PATEL; JONATHAN W. CUNNINGHAM; MUTHIAH VADUGANATHAN; A. M.I.L. SHAH; BRIAN CLAGGETT; SCOTT D. SOLOMON; LAURA RASMUSSEN-TORVIK; LAURA A. COLANGELO; SUZETTE J. BIELINSKI; NICHOLAS B. LARSON; DAVID R. JACOBS; MYRON GROSS; ALEX P. REINER; XIUQING GUO; K. E.N.T. TAYLOR; WENDY S. POST; ALAIN BERTONI; CHRISTIE BALLANTYNE; E. R.I.C. BOERWINKLE; B. I.N.G. YU

Elsevier BV

Medicine

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