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研究确定与动脉完整性和组织介导的凝血有关的风险变异和基因
作者:小柯机器人 发布时间:2023/6/1 11:26:23

法国巴黎西岱大学Nabila Bouatia-Naji等研究人员合作发现,自发性冠状动脉夹层的全基因组关联荟萃分析确定与动脉完整性和组织介导的凝血有关的风险变异和基因。2023年5月29日,《自然—遗传学》杂志在线发表了这项成果。

研究人员提出了一个全基因组关联元分析(1917例病人和9292例对照),确定了自发性冠状动脉夹层(SCAD)的16个风险位点。综合功能注释优先考虑了可能在血管平滑肌细胞和动脉成纤维细胞中被调控,并与细胞外基质生物学有关的基因。一个含有组织因子基因F3的基因座,参与血液凝固级联的启动,似乎对SCAD风险具有特异性。几个相关的变异体与动脉粥样硬化性冠状动脉疾病(CAD)有截然相反的关联,这表明共同的生物过程对两种疾病都有贡献,但机制不同。研究人员还推断出高血压在SCAD中的因果作用。这些发现提供了新的病理生理学见解,涉及SCAD中的动脉完整性和组织介导的凝血,并为未来的特定治疗和预防奠定了基础。

据介绍,SCAD是一个未被充分研究的心肌梗死原因,主要影响妇女。目前还不知道SCAD在多大程度上与其他心血管疾病,包括CAD在遗传上有区别。

附:英文原文

Title: Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation

Author: Adlam, David, Berrandou, Takiy-Eddine, Georges, Adrien, Nelson, Christopher P., Giannoulatou, Eleni, Henry, Josphine, Ma, Lijiang, Blencowe, Montgomery, Turley, Tamiel N., Yang, Min-Lee, Chopade, Sandesh, Finan, Chris, Braund, Peter S., Sadeg-Sayoud, Ines, Iismaa, Siiri E., Kosel, Matthew L., Zhou, Xiang, Hamby, Stephen E., Cheng, Jenny, Liu, Lu, Tarr, Ingrid, Muller, David W. M., dEscamard, Valentina, King, Annette, Brunham, Liam R., Baranowska-Clarke, Ania A., Debette, Stphanie, Amouyel, Philippe, Olin, Jeffrey W., Patil, Snehal, Hesselson, Stephanie E., Junday, Keerat, Kanoni, Stavroula, Aragam, Krishna G., Butterworth, Adam S., Tweet, Marysia S., Gulati, Rajiv, Combaret, Nicolas, Kadian-Dodov, Daniella, Kalman, Jonathan M., Fatkin, Diane, Hingorani, Aroon D., Saw, Jacqueline, Webb, Tom R., Hayes, Sharonne N., Yang, Xia, Ganesh, Santhi K., Olson, Timothy M., Kovacic, Jason C., Graham, Robert M., Samani, Nilesh J., Bouatia-Naji, Nabila

Issue&Volume: 2023-05-29

Abstract: Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

DOI: 10.1038/s41588-023-01410-1

Source: https://www.nature.com/articles/s41588-023-01410-1

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex