Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014 (UP), India.
Cytokine. 2013 Mar;61(3):856-61. doi: 10.1016/j.cyto.2012.12.020. Epub 2013 Jan 26.
Inflammation exacerbates a number of deleterious effects on the heart, most notable being left ventricular dysfunction (LVD). A promoter polymorphism of the NFKB1 gene (encodes p50 subunit) results in lower protein levels of NFkB p50 subunits, which in its dimmer (p50) form has anti-inflammatory effects. The active NFkB transcription factor promotes the expression of over 150 target genes including IL6 and TNF-α. Therefore, the aim of the present study was to assess the association of NFKB1, IL6 and TNF-α gene polymorphisms with LVD in coronary artery disease (CAD) patients.
The present study included a total of 830 subjects (600 CAD patients and 230 controls) and was carried out in two (primary and replication) cohorts. CAD patients with reduced left ventricle ejection fraction (LVEF ≤45%) were categorized having LVD. The NFKB1 -94 ATTG ins/del (rs28362491), IL6 -174 G/C (rs1800795) and TNF-α -308 G/A (rs1800629) polymorphisms were genotyped by PCR/ARMS-PCR methods. The results of the primary cohort were validated in a replicative cohort and pooled by meta-analysis using Fisher's and Mantel-Haenszel test. The analysis showed that NFKB1 ATTG/ATTG genotype was significantly associated with LVD (Fisher's method p-value=0.007, Mantel-Haenszel OR=2.34), LV end diastole (p-value=0.013), end systole (p-value=0.011) dimensions, LV mass (p-value=0.024), mean LVEF (p-value=0.001) and myocardial infarction (p-value=0.043).
Our data suggests that NFKB1 -94 ATTG ins/del polymorphism plays significant role in conferring susceptibility of LVD and ATTG/ATTG genotype may modulate risk of heart failure by increasing ventricular remodeling and worsening LV function.
炎症会加剧对心脏的许多有害影响，最明显的是左心室功能障碍（LVD）。NFKB1 基因（编码 p50 亚基）的启动子多态性导致 NFkB p50 亚基的蛋白水平降低，而 NFkB p50 亚基在其二聚体（p50）形式下具有抗炎作用。活性 NFkB 转录因子促进超过 150 个靶基因的表达，包括 IL6 和 TNF-α。因此，本研究旨在评估 NFKB1、IL6 和 TNF-α 基因多态性与冠心病（CAD）患者 LVD 的相关性。
本研究共纳入 830 例受试者（600 例 CAD 患者和 230 例对照），并分为两个队列（初级和复制队列）进行。左心室射血分数（LVEF≤45%）降低的 CAD 患者被归类为 LVD。NFKB1-94 ATTG ins/del（rs28362491）、IL6-174 G/C（rs1800795）和 TNF-α-308 G/A（rs1800629）多态性通过 PCR/ARMS-PCR 方法进行基因分型。初级队列的结果在复制队列中进行了验证，并通过 Fisher 和 Mantel-Haenszel 检验进行荟萃分析进行了汇总。分析表明，NFKB1 ATTG/ATTG 基因型与 LVD（Fisher 方法 p 值=0.007，Mantel-Haenszel OR=2.34）、LV 舒张末期（p 值=0.013）、收缩末期（p 值=0.011）维度、LV 质量（p 值=0.024）、平均 LVEF（p 值=0.001）和心肌梗死（p 值=0.043）显著相关。
我们的数据表明，NFKB1-94 ATTG ins/del 多态性在赋予 LVD 易感性方面起着重要作用，并且 ATTG/ATTG 基因型可能通过增加心室重构和恶化 LV 功能来增加心力衰竭的风险。
