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

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 (FM...

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Published in:Journal of the American College of Cardiology Vol. 73; no. 1; p. 58
Main Authors: Adlam, David, Olson, Timothy M, Combaret, Nicolas, Kovacic, Jason C, Iismaa, Siiri E, Al-Hussaini, Abtehale, O'Byrne, Megan M, Bouajila, Sara, Georges, Adrien, Mishra, Ketan, Braund, Peter S, d'Escamard, Valentina, Huang, Siying, Margaritis, Marios, Nelson, Christopher P, de Andrade, Mariza, Kadian-Dodov, Daniella, Welch, Catherine A, Mazurkiewicz, Stephani, Jeunemaitre, Xavier, Wong, Claire Mei Yi, Giannoulatou, Eleni, Sweeting, Michael, Muller, David, Wood, Alice, McGrath-Cadell, Lucy, Fatkin, Diane, Dunwoodie, Sally L, Harvey, Richard, Holloway, Cameron, Empana, Jean-Philippe, Jouven, Xavier, Olin, Jeffrey W, Gulati, Rajiv, Tweet, Marysia S, Hayes, Sharonne N, Samani, Nilesh J, Graham, Robert M, Motreff, Pascal, Bouatia-Naji, Nabila
Format: Journal Article
Language:English
Published: United States 08.01.2019
Subjects:
Adult
Aged
Australia
Case-Control Studies
Coronary Vessel Anomalies - complications
Coronary Vessel Anomalies - epidemiology
Coronary Vessel Anomalies - genetics
Endothelin-1 - genetics
Female
Fibromuscular Dysplasia - complications
Fibromuscular Dysplasia - genetics
France
Genetic Loci - genetics
Humans
Male
Microfilament Proteins - genetics
Middle Aged
Prevalence
United Kingdom
United States
Vascular Diseases - complications
Vascular Diseases - congenital
Vascular Diseases - epidemiology
Vascular Diseases - genetics
United Kingdom
Australia
France
United States
cardiovascular disease in women
genetic association
fibromuscular dysplasia
myocardial infarction
ISSN:1558-3597, 1558-3597
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Summary: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. This study sought to test the association between the rs9349379 genotype and SCAD. 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. 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. 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.
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ISSN:1558-3597
1558-3597
DOI:10.1016/j.jacc.2018.09.085