Interleukin-6 serum levels and genotypes influence the risk for myocardial infarction

Objective: Several studies show that the inflammatory component in atherosclerosis may contribute to increased risk for cardiovascular disease (CVD). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-stimulatory cytokine of presumed importance for CVD and the metabolic syndrome. Methods and results: In this case–control study, 1179 surviving myocardial infarction (MI) cases and 1528 healthy controls were genotyped for three IL-6 promoter SNPs, and serum concentrations of IL-6 and C-reactive protein (CRP) were measured. In men, MI risk assessed as odds ratios (OR) was higher with increasing IL-6 levels, with the highest compared to the lowest IL-6 quartiles giving an OR of 2.7 [95% CI 1.7–4.4]. The ORs were independent from the effects of elevated CRP which were associated with modest MI risks (OR=1.6 [95% CI 1.0–2.5]). Also, synergistic interactions between high IL-6 levels and hypercholesterolaemia further increased MI risk estimates. The −174C allele was associated with lower serum-insulin levels among male controls but did not significantly influence MI risk or IL-6 levels. Conclusions: Elevated IL-6 levels are important risk markers for MI in men, the risk being further enhanced through synergistic interaction with hypercholesterolaemia. The data provide no clear evidence that polymorphisms in the IL-6 promotor region play a significant role in the pathogenesis of MI, and it remains to be further evaluated whether or not the −174C allele is of relevance for insulin resistance.