Synergistic effect of anti and pro-inflammatory cytokine genes and their promoter polymorphism with ST-elevation of myocardial infarction.

Abstract

The single-gene approach in association studies of polygenic diseases such as acute myocardial infarction (AMI) is likely to provide limited value. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) plasma levels may be genetically influenced. We evaluate the impact of single nucleotide polymorphism of the promoter region of these genes, as well as reciprocal interaction of these genes with ST-elevation of myocardial infarction (STEMI). In a case-control study 500 STEMI patients and 500 age- and sex-matched controls were studied. Three single-nucleotide polymorphism genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis and assessed their association with STEMI. The synergistic effects of IL-6, TNF-α and IL-10 gene polymorphisms were evaluated by using logistic regression analysis. We found that IL-6 and TNF-α concentrations of studied population were significantly different (p<0.0001) in each genotype of IL-6 -174G>C and TNF-α -308G>A gene polymorphisms respectively. A significant association was found in multivariate analysis for the IL-6 -174G>C [odds ratio (OR): 0.390; 95% confidence interval (CI): 0.176-0.865, p=0.020] and TNF-α -308G>A [OR: 0.372; 95% CI: 0.171-808, p=0.012] gene polymorphisms with STEMI. In contrast, IL-10 -592C>A gene polymorphism was no longer significant in the multivariate model (OR: 0.678; 95% CI: 0.288 to 1.594, p=0.373) whereas significant in univariate analysis (OR: 0.697; 95% CI: 0.523-0.929, p=0.014). Our findings suggest that IL-6, TNF-α and IL-10 gene polymorphisms all contribute in the association with STEMI whereas the association persisted only for IL-6 and TNF-α but not for IL-10 gene polymorphism with this disease in the multivariate analysis.