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. 2019 Jan 8;73(1):58-66.
doi: 10.1016/j.jacc.2018.09.085.

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

David Adlam  1 , Timothy M Olson  2 , Nicolas Combaret  3 , Jason C Kovacic  4 , Siiri E Iismaa  5 , Abtehale Al-Hussaini  6 , Megan M O'Byrne  7 , Sara Bouajila  3 , Adrien Georges  8 , Ketan Mishra  5 , Peter S Braund  6 , Valentina d'Escamard  4 , Siying Huang  8 , Marios Margaritis  6 , Christopher P Nelson  6 , Mariza de Andrade  7 , Daniella Kadian-Dodov  4 , Catherine A Welch  6 , Stephani Mazurkiewicz  8 , Xavier Jeunemaitre  9 ; DISCO Consortium; Claire Mei Yi Wong  5 , Eleni Giannoulatou  5 , Michael Sweeting  6 , David Muller  5 , Alice Wood  6 , Lucy McGrath-Cadell  10 , Diane Fatkin  5 , Sally L Dunwoodie  5 , Richard Harvey  5 , Cameron Holloway  5 , Jean-Philippe Empana  8 , Xavier Jouven  8 ; CARDIoGRAMPlusC4D Study Group; Jeffrey W Olin  4 , Rajiv Gulati  2 , Marysia S Tweet  2 , Sharonne N Hayes  2 , Nilesh J Samani  6 , Robert M Graham  5 , Pascal Motreff  3 , Nabila Bouatia-Naji  11
Collaborators, Affiliations

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

David Adlam et al. J Am Coll Cardiol. .

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.

Keywords: cardiovascular disease in women; fibromuscular dysplasia; genetic association; myocardial infarction.

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Figures

FIGURE 1
FIGURE 1. Forest Plot Shows Associations in individual Studies and the Global Genetic Association Between rs9349379 and SCAD
FIGURE 2
FIGURE 2. Association Between rs9349379 and SCAD Were Compared With the Association Previously Reported Between FMD and CAD/AMI Globally and Those Stratified by Sex
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. Genetic Variant rs9349379 Associates With Spontaneous Coronary Artery Dissection
See this image and copyright information in PMC

Comment in

References

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