Cytokine 2013 Mar 26;61(3):856-61. Epub 2013 Jan 26.
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014 (UP), India.
Rationale: 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.
Methods And Results: 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).
Conclusion: 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.