School of Medicine, Lebanese American University, Beirut, Lebanon.
Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon.
BMC Med Genomics. 2021 Mar 25;14(1):90. doi: 10.1186/s12920-021-00942-x.
Coronary Artery Disease (CAD) is the narrowing or blockage of the coronary arteries. It is closely associated with numerous genetics and environmental factors that have been extensively evaluated in various populations. In recent studies, severe phenotypes have been strongly linked to genetic risk factors.
This study investigated the association of clinical, demographic, and genetic factors with severe coronary artery stenosis phenotypes in our population composed of 1734 individuals with severe coronary stenosis (≥ 50% in coronary vessels) and comparing them to 757 controls with no evidence of stenosis on angiography. We performed generalized linear model (GLM) genome-wide association studies to evaluate three stratification models and their associations to characteristics of the clinical disease. In model 1, patients were not stratified. In model 2, patients were stratified based on presence or absence of CAD family history (FxCAD). In model 3, patients were stratified by young age of CAD onset.
Eight SNPs (single nucleotide polymorphism) were significantly associated with severe CAD phenotypes in the various models [Formula: see text], four of these SNPs were associated with severe CAD and the four others were specifically significant for young CAD patients. While these SNPs were not previously reported for association with CAD, six of them are present in genes that have already been linked to coronary disease.
In conclusion, this study presents new genetic factors associated with severe stenosis and highlights different risk factors associated with a young age at diagnosis of CAD.
冠心病(CAD)是冠状动脉的狭窄或阻塞。它与许多遗传和环境因素密切相关,这些因素已在不同人群中得到广泛评估。在最近的研究中,严重表型与遗传风险因素强烈相关。
本研究调查了临床、人口统计学和遗传因素与我们人群中严重冠状动脉狭窄表型的关联,该人群由 1734 名严重冠状动脉狭窄(冠状动脉血管中≥50%狭窄)患者组成,并将其与 757 名血管造影无狭窄证据的对照者进行比较。我们进行了广义线性模型(GLM)全基因组关联研究,以评估三种分层模型及其与临床疾病特征的关联。在模型 1 中,患者未分层。在模型 2 中,根据是否存在 CAD 家族史(FxCAD)对患者进行分层。在模型 3 中,根据 CAD 发病年龄对患者进行分层。
在不同模型中,有 8 个单核苷酸多态性(SNP)与严重 CAD 表型显著相关[公式:见文本],其中 4 个 SNP 与严重 CAD 相关,另外 4 个 SNP 与年轻 CAD 患者的相关性更显著。虽然这些 SNP 以前没有报道与 CAD 相关,但其中 6 个 SNP 存在于已经与冠状动脉疾病相关的基因中。
总之,本研究提出了与严重狭窄相关的新遗传因素,并强调了与 CAD 诊断年龄较年轻相关的不同危险因素。