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

Thromb Res. 2007;119(4):467-73. doi: 10.1016/j.thromres.2006.05.001. Epub 2006 Jun 16.

Abstract

Background: The concept of inflammation in the acute coronary syndrome (ACS) is today well established. Interleukin-6 (IL-6), a pleiotropic, proinflammatory 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 polymorphisms 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 polymorphisms 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 polymorphisms covered information on approximately 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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Anticoagulants / therapeutic use
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Dalteparin / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Genetic Variation*
  • Humans
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Logistic Models
  • Male
  • Polymorphism, Genetic
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Anticoagulants
  • Interleukin-6
  • C-Reactive Protein
  • Dalteparin