Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection

Adlam, David and Kovacic, Jason C and Iismaa, Siiri E and Al-Hussaini, Abtehale and Wong, Claire Mei Yi and Giannoulatou, Eleni and Sweeting, Michael and Muller, David and Wood, Alice and McGrath-Cadell, Lucy and Fatkin, Diane and Dunwoodie, Sally L and Harvey, Richard and Holloway, Cameron and Empana, Jean-Philippe and Graham, Robert M and Motreff, Pascal and Meneveau, Nicolas and Gilard, Martine and Rioufol, Gilles and Range, Grégoire and Brunel, Philippe and Delarche, Nicolas and Filippi, Emmanuelle and Le Bivic, Louis and Harbaoui, Brahim and Benamer, Hakim and Cayla, Guillaume and Varenne, Olivier and Manzo-Silberman, Stephane Peggy and Silvain, Johanne and Spaulding, Christian and Caussin, Christophe and Gerbaud, Edouard and Valy, Yann and Koning, René and Lhermusier, Thibault and Champin, Stanislas and Salengro, Emmanuel and Fluttaz, Arnaud and Zabalawi, Amer and Cottin, Yves and Teiger, Emmanuel and Saint-Etienne, Christophe and Ducrocq, Grégory and Marliere, Stéphanie and Boiffard, Emmanuel and Aubry, Pierre and Georges, Jean Louis and Benamer, Hakim and Bresson, Didier and De Poli, Fabien and Karrillon, Gaëtan and Roule, Vincent and Bali, Laurent and Valla, Mathieu and Gerbay, Antoine and Houpe, David and Dubreuil, Olivier and Monnier, Arsène and Mayaud, Norbert and Manchuelle, Aurélie and Commeau, Philippe and Bedossa, Marc and Nikpay, Majid and Goel, Anuj and Won, Hong-Hee and Hall, Leanne M. and Willenborg, Christina and Kanoni, Stavroula and Saleheen, Danish and Kyriakou, Theodosios and Nelson, Christopher P. and Hopewell, Jemma C. and Webb, Thomas R. and Zeng, Lingyao and Dehghan, Abbas and Alver, Maris and Armasu, Sebastian M and Auro, Kirsi and Bjonnes, Andrew and Chasman, Daniel I. and Chen, Shufeng and Ford, Ian and Franceschini, Nora and Gieger, Christian and Grace, Christopher and Gustafsson, Stefan and Huang, Jie and Hwang, Shih-Jen and Kim, Yun Kyoung and Kleber, Marcus E. and Lau, King Wai and Lu, Xiangfeng and Lu, Yingchang and Lyytikäinen, Leo P. and Mihailov, Evelin and Morrison, Alanna and Pervjakova, Natalia and Qu, Liming and Rose, Lynda M. and Salfati, Elias and Saxena, Richa and Scholz, Markus and Smith, Albert V. and Tikkanen, Emmi and Uitterlinden, Andre and Yang, Xueli and Zhang, Weihua and Zhao, Wei and de Andrade, Mariza and de Vries, Paul S. and van Zuydam, Natalie R. and Anand, Sonia S. and Bertram, Lars and Beutner, Frank and Dedoussis, George and Frossard, Philippe and Gauguier, Dominique and Goodall, Alison H. and Gottesman, Omri and Haber, Marc and Han, Bok-Ghee and Huang, Jianfeng and Jalilzadeh, Shapour and Kessler, Thorsten and Thiery, Joachim and Zalloua, Pierre A. and O'Donnell, Christopher J. and Reilly, Muredach P. and Assimes, Themistocles L. and Thompson, John R. and Erdmann, Jeanette and Clarke, Robert and Watkins, Hugh and Kathiresan, Sekar and McPherson, Ruth and Deloukas, Panos and Schunkert, Heribert and Samani, Nilesh J. and Farrall, Martin (2019) Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection. Journal of the American College of Cardiology, 73 (1). pp.58-66. ISSN 1558-3597 (Not OA)

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Link to published document: http://doi.org/10.1016/j.jacc.2018.09.085

Abstract

BACKGROUND:

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.
OBJECTIVES:

This study sought to test the association between the rs9349379 genotype and SCAD.
METHODS:

Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.
RESULTS:

The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.
CONCLUSIONS:

The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 16 Jan 2019 02:16
Last Modified: 21 Jan 2019 22:04
URI: https://eprints.victorchang.edu.au/id/eprint/787

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