Related Experiment Videos
The -308 G/A tumor necrosis factor-alpha gene dimorphism: a risk factor for unstable angina
Virginie Bernard1, Xavier Pillois, Isabelle Dubus
1Institut Fédératif de Recherche no 4 Heart-Lung-Vessel-Thrombosis, Institut National de la Santé et de la Recherche Médicale (U441), Pessac, France.
Insights
The tumor necrosis factor-alpha (TNF-alpha) A allele is linked to unstable angina risk, particularly in patients with a lower body mass index. Myocardial infarction risk appears unrelated to this TNF-alpha polymorphism.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Immunology
Background:
- Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are implicated in the pathophysiology of acute coronary syndromes.
- The functional -308G/A TNF-alpha polymorphism is a candidate genetic marker for cardiovascular disease risk.
Purpose of the Study:
- To investigate the association between the -308G/A TNF-alpha polymorphism and the risk of unstable angina and myocardial infarction in male patients with coronary artery disease.
- To explore potential interactions between this polymorphism and clinical factors like body mass index.
Main Methods:
- Genotyping of 299 male patients with coronary artery disease for the -308G/A TNF-alpha polymorphism using restriction fragment length polymorphism.
- Comparison of allele frequencies between patients with unstable angina, myocardial infarction, and stable angina (controls).
- Stratified analysis based on body mass index.
Main Results:
- A significantly higher frequency of the TNF-alpha A allele was observed in patients with unstable angina compared to those with stable angina (39.66% vs. 23.16%, p=0.029).
- No significant association was found between the TNF-alpha A allele and myocardial infarction risk.
- An interaction between the TNF-alpha polymorphism and body mass index was noted, with a stronger association between A allele carriage and unstable angina in patients with a BMI <= 27 (p=0.012).
Conclusions:
- The TNF-alpha -308G/A polymorphism may play a role in the mechanisms underlying unstable angina, potentially related to vulnerable plaque formation.
- The genetic contribution to myocardial infarction appears more complex and heterogeneous, not solely explained by this TNF-alpha polymorphism.
Abstract:
Since the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) may play a major role in the pathophysiology of acute coronary syndromes, 299 consecutive male patients hospitalized for coronary artery disease (i.e., lumen lost > or = 50%) were genotyped for the functional -308G/A TNF-alpha polymorphism using restriction fragment length polymorphism method, in order to evaluate its potential association with the risk of unstable angina and/or myocardial infarction. A higher frequency of carriers of the A allele was observed in patients with unstable angina (n = 58) when compared to control patients with stable angina (n = 95) (39.66% vs. 23.16% respectively, p = 0.029, odds ratio = 2.2) but not in patients with myocardial infarction (n = 146) (23.97% vs. 23.16%, p = NS). Furthermore, we evidenced an interaction of the polymorphism studied with body mass index in patients with unstable angina. Thus, when stratified analysis was performed, results in patients with a body mass index < or = 27 showed a more striking association between A allele carriage frequency and unstable angina (p = 0.012, odds ratio = 3.0). These results suggest the crucial role of TNF-alpha in the mechanisms responsible for unstable angina in accordance with the concept of vulnerable plaque. On the other hand, mechanisms controlling myocardial infarction appear more complex and heterogeneous.