The -308 G/A tumor necrosis factor-alpha gene dimorphism: a risk factor for unstable angina.
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.
Institut Fédératif de Recherche no 4 Heart-Lung-Vessel-Thrombosis, Institut National de la Santé et de la Recherche Médicale (U441), Pessac, France.
Virginie
V
Bernard
Xavier
X
Pillois
Isabelle
I
Dubus
Daniel
D
Benchimol
Jean-Pierre
JP
Labouyrie
Thierry
T
Couffinhal
Pierre
P
Coste
Jacques
J
Bonnet
D000368:Aged; D000483:Alleles; D000787:Angina Pectoris / Q000235:genetics; D000789:Angina, Unstable / Q000235:genetics*; D015992:Body Mass Index; D003324:Coronary Artery Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha