Role of inflammatory gene polymorphisms in left ventricular dysfunction (LVD) susceptibility in coronary artery disease (CAD) patients.
BACKGROUND
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.


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).


CONCLUSIONS
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.
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014 (UP), India.
Avshesh
A
Mishra
Anshika
A
Srivastava
T
T
Mittal
N
N
Garg
B
B
Mittal
D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D011110:Polymorphism, Genetic; D013318:Stroke Volume / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000235:genetics* / Q000503:physiopathology
C508600:IL6 protein, human; D015850:Interleukin-6; D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha