ABSTRACT
BACKGROUND AND OBJECTIVES: A state of low-grade inflammation accompanies the pathogenesis of atherosclerotic events. Interleukin-6 (IL-6) is a pleotropic pro-inflammatory cytokine that modulates the development of acute coronary syndromes (ACSs), partly by destabilizing coronary atherosclerotic plaques. We have examined the contribution of the -174G>C IL-6 promoter variant on the risk of coronary artery disease (CAD) among Tunisians. PATIENTS AND METHODS: Study subjects included 418 CAD patients and 406 age- and sex-matched controls. IL-6 genotyping was done by PCR-restriction fragment length polymorphism. RESULTS: The frequency of the -174C allele (mutant) was lower in Tunisians than in Europeans, and the distribution of -174 G>C genotypes was similar between CAD patients and control subjects. Moreover, compared to GG genotype carriers, -174C allele carriage did not increase the CAD relative risk (odds ratio and 95% confidence interval=1.09 and 0.80-1.49), which remained nonsignificant after adjusting for traditional risk factors for CAD (age, smoking, hypertension, diabetes and obesity). CONCLUSION: The -174G>C IL-6 promoter variant is not associated with an increased risk of CAD among Tunisians.
Subject(s)
Coronary Artery Disease/genetics , Interleukin-6/genetics , Mutation , Polymorphism, Single Nucleotide , Aged , Alleles , Case-Control Studies , Female , Genotype , Humans , Logistic Models , Male , Middle Aged , Promoter Regions, Genetic , Risk Factors , TunisiaABSTRACT
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.
