Acute Disease, Angina, Unstable, Biological Markers, C-Reactive Protein, Clinical Trials as Topic, Coronary Thrombosis, Fibrinogen, Genetic Variation, Genotype, Humans, Inflammation, Interleukin 1 Receptor Antagonist Protein, Interleukin-6, Leukocyte Count, Myocardial Infarction, Polymorphism, Genetic, Recurrence, Risk Factors, Sialoglycoproteins, Syndrome
BACKGROUND: Elevated white blood cell counts (WBC) in acute coronary syndromes (ACS) increase the risk of recurrent events, but it is not known if this is exacerbated by pro-inflammatory factors. We sought to identify whether pro-inflammatory genetic variants contributed to alterations in WBC and C-reactive protein (CRP) in an ACS population.
METHODS: WBC and genotype of interleukin 6 (IL-6 G-174C) and of interleukin-1 receptor antagonist (IL1RN intronic repeat polymorphism) were investigated in 732 Caucasian patients with ACS in the OPUS-TIMI-16 trial. Samples for measurement of WBC and inflammatory factors were taken at baseline, i.e. Within 72 hours of an acute myocardial infarction or an unstable angina event.
RESULTS: An increased white blood cell count (WBC) was associated with an increased C-reactive protein (r = 0.23, p < 0.001) and there was also a positive correlation between levels of beta-fibrinogen and C-reactive protein (r = 0.42, p < 0.0001). IL1RN and IL6 genotypes had no significant impact upon WBC. The difference in median WBC between the two homozygote IL6 genotypes was 0.21/mm3 (95% CI = -0.41, 0.77), and -0.03/mm3 (95% CI = -0.55, 0.86) for IL1RN. Moreover, the composite endpoint was not significantly affected by an interaction between WBC and the IL1 (p = 0.61) or IL6 (p = 0.48) genotype.
CONCLUSIONS: Cytokine pro-inflammatory genetic variants do not influence the increased inflammatory profile of ACS patients.
Byrne CE, Fitzgerald A, Cannon CP, Fitzgerald DJ, Shields DC.Elevated white cell count in acute coronary syndromes: relationship to variants in inflammatory and thrombotic genes. BMC Medical Genetics. 2004;5:13.