Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

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.

PubMed Disclaimer

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

Comment in

References

    1. Hayes SN, Kim ESH, Saw J, et al. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American Heart Association. Circulation 2018;137:e523–57. - PMC - PubMed
    1. Adlam D, Alfonso F, Maas A, Vrints C, Writing Committee. European Society of Cardiology, acute cardiovascular care association, SCAD study group: a position paper on spontaneous coronary artery dissection. Eur Heart J 2018;39:3353–68. - PMC - PubMed
    1. Motreff P, Malcles G, Combaret N, et al. How and when to suspect spontaneous coronary artery dissection: novel insights from a single-centre series on prevalence and angiographic appearance. EuroIntervention 2017;12:e2236–43. - PubMed
    1. Nakashima T, Noguchi T, Haruta S, et al. Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: a report from the angina pectoris-myocardial infarction multicenter investigators in Japan. Int J Cardiol 2016;207:341–8. - PubMed
    1. Rashid HN, Wong DT, Wijesekera H, et al. Incidence and characterisation of spontaneous coronary artery dissection as a cause of acute coronary syndrome—a single-centre Australian experience. Int J Cardiol 2016;202:336–8. - PubMed

Publication types

MeSH terms

Supplementary concepts