-94 ins/del ATTG NFKB1 gene variant is associated with lower susceptibility to myocardial infarction.

BACKGROUND AND AIMS: An imbalance of Nuclear Factor Kappa B (NFкB) and Inhibitor Kappa B (IкB) is involved in various human diseases including atherogenesis. We aimed to evaluate the relationship between NFKB1 and NFKBIA polymorphism and susceptibility to myocardial infarction (MI). METHODS AND RESULTS: Genotyping was performed for NFKB1 and NFKBIA gene variants in 253 subjects (86 patients affected by myocardial infarction and 167 control subjects). In 40 patients, biopsy specimens were taken from the left ventricle area of presumed ischemia for p50, p65 and IкBα quantification. The allele frequency and genotype distribution of NFKBIA gene polymorphism did not differ between MI and control group while control subjects had a higher D allele frequency of -94 ins/del ATTG NFKB1 polymorphism, compared to the MI group (P<0.001; OR=0.304; 95% CI=0.177-0.522). Subjects carrying the D allele had significantly lower plasma fibrinogen and CRP (C-reactive protein) levels compared to no carriers (P<0.05). Fibrinogen-genotype interaction was found to have a significant effect on susceptibility to myocardial infarction. Myocardial p50 (r=0.627; P=0.012) and p65 (r=0.683; P=0.005) levels significantly correlated with plasma fibrinogen levels while subjects carrying the D allele of the NFкB1 gene variant had lower myocardial p50 (P=0.007) and p65 (P=0.009) levels compared to no carriers. CONCLUSION: -94 ins/del ATTG NFKB1 gene variant may contribute to lower MI susceptibility via the potential reduction of activated NFкB which in turn is related to plasma inflammatory marker reduction.