Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation

Paolo Severino; Andrea D’Amato; Silvia Prosperi; Michele Magnocavallo; Marco Valerio Mariani; Lucrezia Netti; Lucia Ilaria Birtolo; Paolo De Orchi; Cristina Chimenti; Viviana Maestrini; Fabio Miraldi; Carlo Lavalle; Viviana Caputo; Raffaele Palmirotta; Massimo Mancone; Francesco Fedele

doi:10.3390/jcdd8090116

Journal of Cardiovascular Development and Disease (Sep 2021)

Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation

Paolo Severino,
Andrea D’Amato,
Silvia Prosperi,
Michele Magnocavallo,
Marco Valerio Mariani,
Lucrezia Netti,
Lucia Ilaria Birtolo,
Paolo De Orchi,
Cristina Chimenti,
Viviana Maestrini,
Fabio Miraldi,
Carlo Lavalle,
Viviana Caputo,
Raffaele Palmirotta,
Massimo Mancone,
Francesco Fedele

Affiliations

Paolo Severino: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Andrea D’Amato: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Silvia Prosperi: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Michele Magnocavallo: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Marco Valerio Mariani: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Lucrezia Netti: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Lucia Ilaria Birtolo: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Paolo De Orchi: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Cristina Chimenti: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Viviana Maestrini: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Fabio Miraldi: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Carlo Lavalle: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Viviana Caputo: Department of Experimental Medicine, Sapienza University of Rome, Policlinico Umberto I Hospital, Viale Regina Elena 324, 00161 Rome, Italy
Raffaele Palmirotta: Interdisciplinary Department of Medicine, School of Medicine, University of Bari ‘Aldo Moro’, 70124 Bari, Italy
Massimo Mancone: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Francesco Fedele: Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy

DOI: https://doi.org/10.3390/jcdd8090116
Journal volume & issue: Vol. 8, no. 9
p. 116

Abstract

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Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Published in Journal of Cardiovascular Development and Disease

ISSN: 2308-3425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: http://www.mdpi.com/journal/jcdd

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