2023-05-30 ニューサウスウェールズ大学(UNSW)
◆研究者は、SCADに関連する少なくとも16の遺伝子があり、PHACTR1という遺伝子が主な要因であると考えられています。これにより、SCADの原因となる遺伝子が特定され、冠動脈を構成する細胞の周りのマトリックスや足場形成に関与する遺伝子、血液凝固に関与する遺伝子が明らかになりました。
◆この研究はSCADの遺伝的リスクと他の心血管疾患との関連性をより明確にし、新しいアプローチを通じて管理と治療の手段を見つけることにつながると期待されています。また、研究者たちは国際的な共同研究であるiSCAD Registryに参加し、SCADの特徴と病態生理学を調査しています。この登録には、これまで米国の患者の医療記録が含まれており、オーストラリアの患者もデータを提供する予定です。
<関連情報>
- https://newsroom.unsw.edu.au/news/health/pinpointing-cause-mysterious-heart-disease-affecting-women
- https://www.nature.com/articles/s41588-023-01410-1
自然発症冠動脈解離のゲノムワイド関連メタ解析により、リスクバリアントと動脈の完全性と組織媒介性凝固に関連する遺伝子が特定される Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
David Adlam,Takiy-Eddine Berrandou,Adrien Georges,Christopher P. Nelson,Eleni Giannoulatou,Joséphine Henry,Lijiang Ma,Montgomery Blencowe,Tamiel N. Turley,Min-Lee Yang,Sandesh Chopade,Chris Finan,Peter S. Braund,Ines Sadeg-Sayoud,Siiri E. Iismaa,Matthew L. Kosel,Xiang Zhou,Stephen E. Hamby,Jenny Cheng,Lu Liu,Ingrid Tarr,David W. M. Muller,Valentina d’Escamard,Annette King,Liam R. Brunham,Ania A. Baranowska-Clarke,Stéphanie Debette,Philippe Amouyel,Jeffrey W. Olin,Snehal Patil,Stephanie E. Hesselson,Keerat Junday,Stavroula Kanoni,Krishna G. Aragam,Adam S. Butterworth,CARDIoGRAMPlusC4D,MEGASTROKE,International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group,Marysia S. Tweet,Rajiv Gulati,Nicolas Combaret,DISCO register,Daniella Kadian-Dodov,Jonathan M. Kalman,Diane Fatkin,Aroon D. Hingorani,Jacqueline Saw,Tom R. Webb,Sharonne N. Hayes,Xia Yang,Santhi K. Ganesh,Timothy M. Olson,Jason C. Kovacic,Robert M. Graham,Nilesh J. Samani & Nabila Bouatia-Naji
Nature Genetics Published:29 May 2023
DOI:https://doi.org/10.1038/s41588-023-01410-1
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.
