Association of IL1B polymorphism with left ventricular systolic dysfunction: a relation with the release of interleukin-1β in stress condition
Association of IL1B polymorphism with left ventricular systolic dysfunction: a relation with the release of interleukin-1β in stress condition
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DOI：
10.1097/fpc.0b013e3283493a05
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发表时间：
2011-09-01
影响因子：
2.6
通讯作者：
Gueant, Jean-Louis
中科院分区：
文献类型：
--
作者：
Gueant-Rodriguez, Rosa-Maria;Juilliere, Yves;Gueant, Jean-Louis
目的促炎细胞因子在心力衰竭的发病机制中起重要作用。此外，尽管心理应激对交感神经刺激白介素1β(IL-1β)的分泌有影响，但关于它对心力衰竭的影响的文献报道很少。我们在572例因冠状动脉造影术产生精神应激的患者中，研究了促炎细胞因子基因多态性是否可以预测左心室收缩功能不全(LVSD)，如果是，这种关联是否与这些细胞因子的分泌有关。方法根据左心室射血分数(LVSD)，我们检测IL-1RN(VNTR)、IL1A-889 C&gT；T、IL1B-511 C&gT；T、IL6-174 G>；C和TNFA-308 G&gT；A。分别在基础状态(T0和T2，冠状动脉造影前、后)和应激状态(T1)检测患者唾液IL-1β、血清肿瘤坏死因子-α和C反应蛋白。主要结果42.1%的LVSD患者IL-1B T等位基因频率是对照组的1.50倍(P<0.001)。IL1B-511TT与LVSD相关(P=0.008)，与T1时唾液IL-1β水平降低相关(P=0.013)。IL-1β在T1时最高(P<0.001)，并与左心室射血分数相关(P=0.002)。多因素分析显示，IL1B基因TT型和C反应蛋白是左室肥厚的两个独立预测因子，其OR值分别为2.7(95%可信区间：1.3~5.5；P=0.008)和1.1(95%可信区间：1.1~1.2；P<0.001)。提示IL-1B通过影响IL-1β的分泌而影响LVSD。药物遗传学和基因组学21：579-586(C)2011 Wolters Kluwer Health|Lippincott Williams&Wilkins。
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.