-308G>A and -1031T>C tumor necrosis factor gene polymorphisms in Tunisian patients with coronary artery disease.

Background: Recent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Several lines of evidence support a key role for tumor necrosis factor-alpha (TNF-alpha), a potent immunomodulator and pro-inflammatory cytokine, in the development of atherosclerosis and in complications of CAD.

Methods: We investigated the possible association between CAD and the TNF gene promoter polymorphisms -308G>A and -1031T>C in a Tunisian population. We compared the distribution of these polymorphisms between 418 patients with CAD and 406 healthy controls using polymerase chain reaction restriction fragment length-polymorphism analysis.

Results: The frequency of the TNF-alpha -308A allele in the control group was similar to that observed in CAD patients [p=0.78; odds ratio (OR)=1.15; 95% confidence interval (CI)=0.86-1.55], but higher than those described in other Europeans, such as in the French, Finnish and Spanish. Concerning the TNF-alpha -1031T/C polymorphism, the same distribution was observed between patients with CAD and controls (p=0.12; OR=1.27; 95% CI=0.94-1.72). In addition, the genotype and allele frequencies of control individuals were comparable to those previously reported in healthy Tunisian controls and other ethnic groups. Haplotype analysis (TNF-alpha -308G>A and -1031T>C) demonstrated no significant association between TNF haplotypes and CAD.

Conclusions: We conclude that TNF promoter gene polymorphisms at position -308G>A and -1031T>C do not play a major role in the pathogenesis of CAD in the Tunisian population.