Association of IL1B polymorphism with left ventricular systolic dysfunction: a relation with the release of interleukin-1β in stress condition

Objective Proinflammatory cytokines play a major role in the pathomechanisms of heart failure. Besides this, the influence of mental stress on heart failure is poorly documented despite its effects on sympathetic stimulation of interleukin-1 beta (IL-1 beta) secretion. We examined whether the polymorphisms of proinflammatory cytokines are predictors of left ventricular systolic dysfunction (LVSD) and if so, whether such associations are related to the secretion of these cytokines, in 572 consecutive patients under mental stress produced by coronary angiography. Methods We examined IL-1RN (VNTR), IL1A-889 C > T, IL1B-511 C > T, IL6-174 G > C and TNFA-308 G > A, according to LVSD (left ventricular ejection fraction, < 40%). Saliva IL-1 beta, serum tumour necrosis factor-alpha and C-reactive protein were assayed in basal (T0 and T2, before and after coronary angiography) and stress (T1) conditions. Main results The 42.1% of patients with LVSD had a 1.5-fold higher frequency of IL1B T allele (P < 0.001). IL1B-511TT was associated with LVSD (P = 0.008) and with a decrease in IL-1 beta level in saliva at T1 (P = 0.013). IL-1 beta was the highest at T1 (P < 0.001) and was associated with left ventricular ejection fraction (P = 0.002). The IL1B TT genotype and the C-reactive protein were the two independent predictors of LVSD in multivariate analysis, with an odds ratio of 2.7 (95% confidence interval: 1.3-5.5; P = 0.008) and 1.1 (95% confidence interval: 1.1-1.2; P < 0.001), respectively. Conclusion IL1B was a predictor of LVSD and of the decreased IL-1 beta response to stress. This suggests that IL1B exerts an influence on LVSD through its effect on IL-1 beta secretion. Pharmacogenetics and Genomics 21:579-586 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.