Acute coronary syndromes (ACSs) are associated with both systemic inflammatory activation and endothelial cell activation, and both of these are linked to patient outcome. Genetic variation at the interleukin-1 (IL-1) locus influences the clinical patterns of inflammatory disease. We therefore examined the association between IL-1 gene polymorphisms and levels of systemic inflammatory activation markers [C-reactive protein (CRP) and IL-1 receptor antagonist (IL-1ra)] and of soluble endothelial activation markers [von Willebrand factor (vWF) and E-selectin], in a cohort of 63 patients presenting with non-ST-elevation ACS. The IL-1 locus did not significantly influence any of the markers studied at 24h after presentation. Associations of IL-1 polymorphisms with the changes (Δ) in CRP, IL-1ra, E-selectin and vWF levels between 24 and 48h were examined in later studies. ΔCRP and ΔIL-1ra showed no significant association with any of the polymorphisms studied. There was a strong association between carriage of the rare allele (allele 2) of the intron 2 variable number of tandem repeats polymorphism of IL-1RN (designated IL-1RN*2) and ΔE-selectin levels: {carriage of *2, 3.03 ng/ml [95% confidence interval (CI) 6.26 to 1.51ng/ml]; non-carriage of *2, 0.12ng/ml (95% CI 1.07 to -1.76ng/ml); P = 0.0016}, and also between carriage of IL-1RN*2 and ΔvWF levels [carriage of *2, 0.78i.u./ml (95% CI 0.96 to 0.44i.u./ml); non-carriage of *2, 0.1i.u./ml (95% CI 0.19 to -0.1i.u./ml); P = 0.0003]. A composite analysis consisting of carriage of IL-1RN*2 and the genotype at position -511 in the IL-1B gene suggests the existence of haplotypes that influence ΔvWF and ΔE-selectin in patients with ACS. Carriage of IL-1RN*2 was also associated with a 2-fold increased likelihood of a troponin-positive status compared with non-carriage (P = 0.0385). These data indicate that, in the setting of non-ST-elevation ACS, genetic variation at the IL-1 gene locus contributes to the changes in soluble markers of endothelial inflammation.

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