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Potential Role of eNOS Genetic Variants in Ischemic Heart Disease Susceptibility and Clinical Presentation
Paolo Severino1, Andrea D'Amato1, Silvia Prosperi1
1Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Insights
The eNOS rs1799983_GT genetic variant is an independent risk factor for ischemic heart disease (IHD) and acute coronary syndrome (ACS). This finding aids in predicting IHD development and identifying high-risk patients for early intervention.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Endothelial Function
Background:
- Ischemic heart disease (IHD) involves inadequate coronary blood supply, with endothelial dysfunction as a key mechanism.
- Genetic predisposition to endothelial dysfunction is linked to IHD, but studies face confounding factors like interethnic differences.
- Further validation in diverse populations is crucial for understanding genetic associations with IHD.
Purpose of the Study:
- To investigate the association between eNOS rs1799983 single-nucleotide polymorphism (SNP) allelic variants and IHD susceptibility.
- To evaluate the relationship between these variants and the clinical presentation of IHD.
- To assess the predictive value of eNOS variants for IHD and acute coronary syndrome (ACS).
Main Methods:
- Analysis of 362 patients with suspected myocardial ischemia, categorized into coronary artery disease (CAD), coronary microvascular dysfunction (CMD), and control groups.
- Genotyping of three allelic variants (GT, GG, TT) of the NOS3 gene rs1799983 polymorphism, which encodes endothelial nitric oxide synthase (eNOS).
- Multivariate analysis to determine independent predictors of IHD and ACS presentation.
Main Results:
- The rs1799983_GT variant was significantly more prevalent in ischemic groups (CAD and CMD) compared to controls.
- The TT variant was more frequent in the CAD group than in the CMD group.
- Among ischemic patients, the GT variant was more common in those with ACS presentation and identified as an independent predictor of IHD and ACS.
Conclusions:
- The eNOS rs1799983_GT SNP is an independent risk factor for IHD and ACS, irrespective of other cardiovascular risk factors.
- These findings support the use of rs1799983 genotyping for predicting IHD development, especially acute presentations.
- This genetic marker may enable early identification of high-risk individuals, facilitating personalized, gene-based prevention strategies for IHD.
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.
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