Missense Genetic Variation of ICAM1 and Incident Heart Failure.
J Card Fail
; 29(8): 1163-1172, 2023 08.
Article
em En
| MEDLINE
| ID: mdl-36882149
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 ANDRESULTS:
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 (nâ¯=â¯1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HRâ¯=â¯2.30; [95% CI 1.25-4.21; Pâ¯=â¯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 (HRâ¯=â¯1.24 [95% CI 1.02 - 1.51]; Pâ¯=â¯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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aterosclerose
/
Insuficiência Cardíaca
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article