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

• Anti (IL-10) and pro-inflammatory (IL-6 & TNFα) cytokine gene SNPs with STEMI
• Effects of these polymorphisms were evaluated by using logistic regression analysis.
• IL-6 and TNF-α concentrations were significantly different in each genotype.
• In univariate analysis all three genes were significantly associated with STEMI.
• Only the proinflammatory cytokine genes were significant in multivariate analysis.

BackgroundThe 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.AimWe 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).MethodsIn 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.ResultsWe 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).ConclusionsOur 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.