Missense Genetic Variation of ICAM1 and Incident Heart Failure

Authors

Pedro Giro
Jonathan W Cunningham
Laura Rasmussen-Torvik
Suzette J Bielinski
Nicholas B Larson
Laura A Colangelo
David R Jacobs
Myron Gross
Alex P Reiner
Donald M Lloyd-Jones
Xiuqing Guo
Kent Taylor
Muthiah Vaduganathan
Wendy S Post
Alain Bertoni
Christie Ballantyne
Amil Shah
Brian Claggett
Eric Boerwinkle
Bing Yu
Scott D Solomon
Sanjiv J Shah
Ravi B Patel

Publication Date

8-1-2023

Journal

Journal of Cardiac Failure

Abstract

BACKGROUND: 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.

METHODS AND RESULTS: 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.

CONCLUSIONS: A common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.

Keywords

Young Adult, Humans, Heart Failure, Intercellular Adhesion Molecule-1, Stroke Volume, Atherosclerosis, Genetic Variation, intercellular adhesion molecule-1, race/ethnicity, genetics, heart failure, rs5491

DOI

10.1016/j.cardfail.2023.02.003

PMID

36882149

PMCID

PMC10477308

PubMedCentral® Posted Date

8-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes