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.

Potential role of eNOS genetic variants in ischemic heart disease susceptibility and clinical presentation / Severino, Paolo; D'Amato, Andrea; Prosperi, Silvia; Magnocavallo, Michele; Mariani, Marco Valerio; Netti, Lucrezia; Birtolo, Lucia Ilaria; De Orchi, Paolo; Chimenti, Cristina; Maestrini, Viviana; Miraldi, Fabio; Lavalle, Carlo; Caputo, Viviana; Palmirotta, Raffaele; Mancone, Massimo; Fedele, Francesco. - In: JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE. - ISSN 2308-3425. - 8:9(2021). [10.3390/jcdd8090116]

Potential role of eNOS genetic variants in ischemic heart disease susceptibility and clinical presentation

Severino, Paolo
Co-primo
;
D'Amato, Andrea
Co-primo
;
Prosperi, Silvia;Magnocavallo, Michele;Mariani, Marco Valerio;Netti, Lucrezia;Birtolo, Lucia Ilaria;De Orchi, Paolo;Chimenti, Cristina;Maestrini, Viviana;Miraldi, Fabio;Lavalle, Carlo;Caputo, Viviana;Palmirotta, Raffaele;Mancone, Massimo
Penultimo
;
Fedele, Francesco
Ultimo
2021

Abstract

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.
File allegati a questo prodotto
File Dimensione Formato  
Severino_Potential Role_2021.pdf

accesso aperto

Note: https://www.mdpi.com/2308-3425/8/9/116
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 718.41 kB
Formato Adobe PDF
718.41 kB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1571574
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 7
social impact