Genetic variation in the interleukin-6 gene in relation to risk and outcomes in acute coronary syndrome

Background: The concept of inflammation in the acute coronary syndrome (ACS) is today well established. Interleukin-6 (IL-6), a pleiotropic, proinftammatory cytokine, seems to play an important role in the development and progression of ACS. Aim. The aim was to investigate whether IL6 polymorphisms are associated with patient/control status, outcome in patients with ACS and plasma concentrations of IL-6 and C-reactive protein (CRP). Methods: Samples for citrated plasma and DNA were obtained on admission from 3027 patients with non-ST-elevation ACS in the FRISC-II study. A group of 447 healthy controls of similar age and gender as the patients was also recruited. Eight IL6 potymorphisms were genotyped and plasma concentrations of IL-6 and CRP measured in patients and controls. Results: No associations between patient/control status, clinical outcome, ST-depression, troponin-T elevation or a history of myocardial infarction and IL6 potymorphisms were observed. In the full patient group, there was a trend towards association of the -572 G > C polymorphism with plasma concentrations of IL-6 (p=0.07). This association was statistically significant in patients with available high-sensitivity measurements of IL-6 (p=0.01). The -572 CG genotype was predictive for IL-6 levels above 5 ng/L in patients with a subsequent cardiovascular event, 2.3 (1.1-4.3) (adjusted odds ratio, 95% confidence interval). Comparison with data from HapMap showed that our panel of potymorphisms covered information on similar to 30 other IL6 variants. Conclusion: The -572 G > C and other polymorphisms in the study were not associated with outcome in ACS patients. However, the -572 CG genotype may contribute to a more distinct inflammatory response in patients with ACS. (c) 2006 Elsevier Ltd. All rights reserved.