title: Association of IL1B polymorphism with left ventricular systolic dysfunction: a relation with the release of interleukin-1β in stress condition.
abstract: 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-1β (IL-1β) 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-1β, serum tumour necrosis factor-α and C-reactive protein were assayed in basal (T0 and T2, before and after coronary angiography) and stress (T1) conditions.
  
  
  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-1β level in saliva at T1 (P=0.013). IL-1β 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.
  
  
  CONCLUSIONS
  IL1B was a predictor of LVSD and of the decreased IL-1β response to stress. This suggests that IL1B exerts an influence on LVSD through its effect on IL-1β secretion.
authors.affiliation: Nutrition, Genetics and Environment, INSERM-U954, Faculty of Medicine, Vandoeuvre lès Nancy, Nancy, France. rm.rodriguez@chu-nancy.fr
authors.forename: Rosa-Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: Yves
authors.initials: Y
authors.lastname: Juillière
authors.forename: Shyue-Fang
authors.initials: SF
authors.lastname: Battaglia-Hsu
authors.forename: Renée
authors.initials: R
authors.lastname: Debard
authors.forename: Philippe
authors.initials: P
authors.lastname: Gérard
authors.forename: Pedro
authors.initials: P
authors.lastname: Reyes
authors.forename: Nicolas
authors.initials: N
authors.lastname: Danchin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000368:Aged; D017023:Coronary Angiography / Q000009:adverse effects; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013312:Stress, Physiological / Q000235:genetics; D013599:Systole / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000235:genetics*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta