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 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
08.01.2019
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| Subjects: | |
| ISSN: | 1558-3597, 1558-3597 |
| Online Access: | Get more information |
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| Abstract | 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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| AbstractList | 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.BACKGROUNDSpontaneous 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.OBJECTIVESThis 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.METHODSResults 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.RESULTSThe 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.CONCLUSIONSThe 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. 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. |
| Author | de Andrade, Mariza Nelson, Christopher P Bouatia-Naji, Nabila Tweet, Marysia S Empana, Jean-Philippe Combaret, Nicolas Jouven, Xavier Hayes, Sharonne N Harvey, Richard Mishra, Ketan Motreff, Pascal Margaritis, Marios Welch, Catherine A d'Escamard, Valentina Wood, Alice Iismaa, Siiri E Adlam, David Kadian-Dodov, Daniella Graham, Robert M Al-Hussaini, Abtehale Mazurkiewicz, Stephani Muller, David Huang, Siying Samani, Nilesh J Jeunemaitre, Xavier Holloway, Cameron Fatkin, Diane Gulati, Rajiv Dunwoodie, Sally L Giannoulatou, Eleni Wong, Claire Mei Yi Bouajila, Sara Georges, Adrien Braund, Peter S Kovacic, Jason C Sweeting, Michael Olin, Jeffrey W O'Byrne, Megan M McGrath-Cadell, Lucy Olson, Timothy M |
| Author_xml | – sequence: 1 givenname: David surname: Adlam fullname: Adlam, David email: da134@le.ac.uk organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom. Electronic address: da134@le.ac.uk – sequence: 2 givenname: Timothy M surname: Olson fullname: Olson, Timothy M organization: Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota – sequence: 3 givenname: Nicolas surname: Combaret fullname: Combaret, Nicolas organization: Department of Cardiology, University Hospital of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France – sequence: 4 givenname: Jason C surname: Kovacic fullname: Kovacic, Jason C organization: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, New York, New York – sequence: 5 givenname: Siiri E surname: Iismaa fullname: Iismaa, Siiri E organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 6 givenname: Abtehale surname: Al-Hussaini fullname: Al-Hussaini, Abtehale organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 7 givenname: Megan M surname: O'Byrne fullname: O'Byrne, Megan M organization: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota – sequence: 8 givenname: Sara surname: Bouajila fullname: Bouajila, Sara organization: Department of Cardiology, University Hospital of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France – sequence: 9 givenname: Adrien surname: Georges fullname: Georges, Adrien organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France – sequence: 10 givenname: Ketan surname: Mishra fullname: Mishra, Ketan organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 11 givenname: Peter S surname: Braund fullname: Braund, Peter S organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 12 givenname: Valentina surname: d'Escamard fullname: d'Escamard, Valentina organization: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, New York, New York – sequence: 13 givenname: Siying surname: Huang fullname: Huang, Siying organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France – sequence: 14 givenname: Marios surname: Margaritis fullname: Margaritis, Marios organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 15 givenname: Christopher P surname: Nelson fullname: Nelson, Christopher P organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 16 givenname: Mariza surname: de Andrade fullname: de Andrade, Mariza organization: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota – sequence: 17 givenname: Daniella surname: Kadian-Dodov fullname: Kadian-Dodov, Daniella organization: The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, New York, New York – sequence: 18 givenname: Catherine A surname: Welch fullname: Welch, Catherine A organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 19 givenname: Stephani surname: Mazurkiewicz fullname: Mazurkiewicz, Stephani organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France – sequence: 20 givenname: Xavier surname: Jeunemaitre fullname: Jeunemaitre, Xavier organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France; Department of Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France – sequence: 21 givenname: Claire Mei Yi surname: Wong fullname: Wong, Claire Mei Yi organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 22 givenname: Eleni surname: Giannoulatou fullname: Giannoulatou, Eleni organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 23 givenname: Michael surname: Sweeting fullname: Sweeting, Michael organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 24 givenname: David surname: Muller fullname: Muller, David organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 25 givenname: Alice surname: Wood fullname: Wood, Alice organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 26 givenname: Lucy surname: McGrath-Cadell fullname: McGrath-Cadell, Lucy organization: St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 27 givenname: Diane surname: Fatkin fullname: Fatkin, Diane organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 28 givenname: Sally L surname: Dunwoodie fullname: Dunwoodie, Sally L organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 29 givenname: Richard surname: Harvey fullname: Harvey, Richard organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 30 givenname: Cameron surname: Holloway fullname: Holloway, Cameron organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 31 givenname: Jean-Philippe surname: Empana fullname: Empana, Jean-Philippe organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France – sequence: 32 givenname: Xavier surname: Jouven fullname: Jouven, Xavier organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France – sequence: 33 givenname: Jeffrey W surname: Olin fullname: Olin, Jeffrey W organization: The Zena and Michael A. 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Kravis Cardiovascular Health Center at Mount Sinai, New York, New York – sequence: 34 givenname: Rajiv surname: Gulati fullname: Gulati, Rajiv organization: Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota – sequence: 35 givenname: Marysia S surname: Tweet fullname: Tweet, Marysia S organization: Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota – sequence: 36 givenname: Sharonne N surname: Hayes fullname: Hayes, Sharonne N organization: Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota – sequence: 37 givenname: Nilesh J surname: Samani fullname: Samani, Nilesh J organization: Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom – sequence: 38 givenname: Robert M surname: Graham fullname: Graham, Robert M organization: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia – sequence: 39 givenname: Pascal surname: Motreff fullname: Motreff, Pascal organization: Department of Cardiology, University Hospital of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France – sequence: 40 givenname: Nabila surname: Bouatia-Naji fullname: Bouatia-Naji, Nabila email: nabila.bouatia-naji@inserm.fr organization: INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France. Electronic address: nabila.bouatia-naji@inserm.fr |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30621952$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Contributor | Gerbay, Antoine de Andrade, Mariza Bedossa, Marc Uitterlinden, Andre Aubry, Pierre Nelson, Christopher P Hwang, Shih-Jen Bali, Laurent Mihailov, Evelin Brunel, Philippe Franceschini, Nora van Zuydam, Natalie R Hall, Leanne M Kim, Yun Kyoung Spaulding, Christian Champin, Stanislas Tikkanen, Emmi Alver, Maris Roule, Vincent Cayla, Guillaume Webb, Thomas R Zabalawi, Amer Lyytikäinen, Leo P Gerbaud, Edouard Karrillon, Gaëtan Koning, René Nikpay, Majid Belle, Loïc Dubreuil, Olivier Motreff, Pascal Dehghan, Abbas Barnay, Pierre Gustafsson, Stefan Auro, Kirsi Boiffard, Emmanuel Gieger, Christian Kleber, Marcus E de Vries, Paul S Zhao, Wei Lu, Xiangfeng Benamer, Hakim Rose, Lynda M Delarche, Nicolas Smith, Albert V Dupouy, Patrick Pervjakova, Natalia Lhermusier, Thibault Bresson, Didier Lau, King Wai Rioufol, Gilles Willenborg, Christina Goel, Anuj Zeng, Lingyao Mayaud, Norbert Silvain, Johanne Commeau, Philippe Qu, Liming Le Bivic, Louis Ducrocq, Grégory Kyriakou, Theodosios Manzo-Silberman, Stephane Peggy Morrison, Alanna Valy, Yann Varenne, Olivier Chas |
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| Copyright | Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
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| Keywords | cardiovascular disease in women genetic association fibromuscular dysplasia myocardial infarction |
| Language | English |
| License | Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
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| References | 30621953 - J Am Coll Cardiol. 2019 Jan 8;73(1):67-69. doi: 10.1016/j.jacc.2018.10.046. |
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| Snippet | Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to... |
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| SubjectTerms | 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 |
| Title | Association of the PHACTR1/EDN1 Genetic Locus With Spontaneous Coronary Artery Dissection |
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