From the Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.
Division of Cardiology, Department of Medicine, Brigham and Woman's Hospital, Boston, MA.
J Card Fail. 2023 Aug;29(8):1163-1172. doi: 10.1016/j.cardfail.2023.02.003. Epub 2023 Mar 5.
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.
细胞间黏附分子-1（ICAM-1）是一种细胞表面蛋白，参与内皮细胞激活，被认为在心力衰竭（HF）中起核心作用。我们评估了 ICAM1 错义遗传变异与循环 ICAM-1 水平以及 HF 事件的相关性。
我们在 ICAM1 中鉴定了 3 个错义变异（rs5491、rs5498 和 rs1799969），并在年轻成年人冠状动脉风险发展研究（CARDIA）和动脉粥样硬化多民族研究（MESA）中评估了它们与 ICAM-1 水平的关系。我们确定了这 3 个变异与 MESA 中 HF 事件的关联。我们分别在社区动脉粥样硬化风险研究（ARIC）中评估了显著的关联。在 3 个错义变异中，rs5491 在黑人群体中很常见（次要等位基因频率[MAF]＞20%），而在其他种族/族裔群体中很少见（MAF＜5%）。在黑人群体中，rs5491 的存在与 8 年内 2 个时间点的循环 ICAM-1 水平升高有关。在 MESA 的黑人群体（n=1600）中，rs5491 的存在与射血分数保留的 HF（HFpEF；HR=2.30；95%CI 1.25-4.21；P=0.007）的 HF 事件风险增加有关。其他的 ICAM1 错义变异（rs5498 和 rs1799969）与 ICAM-1 水平相关，但与 HF 无关。在 ARIC 中，rs5491 与 HF 事件显著相关（HR=1.24；95%CI 1.02-1.51；P=0.03），HFpEF 的效应方向相似，但无统计学意义。
黑人群体中常见的 ICAM1 错义变异可能与 HF 风险增加有关，这可能是 HFpEF 特异性的。
