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.
RCT Entities:
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.
Authors: Christine Miaskowski; Marylin Dodd; Kathryn Lee; Claudia West; Steven M Paul; Bruce A Cooper; William Wara; Patrick S Swift; Laura B Dunn; Bradley E Aouizerat Journal: J Pain Symptom Manage Date: 2010-06-08 Impact factor: 3.612
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Authors: Benjamin P Fairfax; Fredrik O Vannberg; Jayachandran Radhakrishnan; Hakon Hakonarson; Brendan J Keating; Adrian V S Hill; Julian C Knight Journal: Hum Mol Genet Date: 2009-11-26 Impact factor: 6.150