Missense Genetic Variation of ICAM1 and Incident Heart Failure

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, K. E.N.T. TAYLOR, MUTHIAH VADUGANATHAN, WENDY S. POST, ALAIN BERTONI, CHRISTIE BALLANTYNE, A. M.I.L. SHAH, BRIAN CLAGGETT, E. R.I.C. BOERWINKLE, B. I.N.G. YUSCOTT D. SOLOMON, SANJIV J. SHAH, RAVI B. PATEL

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1163-1172
Number of pages10
JournalJournal of cardiac failure
Volume29
Issue number8
DOIs
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

  • Intercellular adhesion molecule-1
  • genetics
  • heart failure
  • race/ethnicity
  • rs5491

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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