TY - JOUR
T1 - Missense Genetic Variation of ICAM1 and Incident Heart Failure
AU - Giro, PEDRO
AU - CUNNINGHAM, JONATHAN W.
AU - RASMUSSEN-TORVIK, LAURA
AU - BIELINSKI, SUZETTE J.
AU - LARSON, NICHOLAS B.
AU - COLANGELO, LAURA A.
AU - JACOBS, DAVID R.
AU - GROSS, MYRON
AU - REINER, ALEX P.
AU - LLOYD-JONES, DONALD M.
AU - GUO, XIUQING
AU - TAYLOR, K. E.N.T.
AU - VADUGANATHAN, MUTHIAH
AU - POST, WENDY S.
AU - BERTONI, ALAIN
AU - BALLANTYNE, CHRISTIE
AU - SHAH, A. M.I.L.
AU - CLAGGETT, BRIAN
AU - BOERWINKLE, E. R.I.C.
AU - YU, B. I.N.G.
AU - SOLOMON, SCOTT D.
AU - SHAH, SANJIV J.
AU - PATEL, RAVI B.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/8
Y1 - 2023/8
N2 - 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.
AB - 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.
KW - Intercellular adhesion molecule-1
KW - genetics
KW - heart failure
KW - race/ethnicity
KW - rs5491
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U2 - 10.1016/j.cardfail.2023.02.003
DO - 10.1016/j.cardfail.2023.02.003
M3 - Article
C2 - 36882149
AN - SCOPUS:85151412455
SN - 1071-9164
VL - 29
SP - 1163
EP - 1172
JO - Journal of cardiac failure
JF - Journal of cardiac failure
IS - 8
ER -