Nuclear Factor (NF) kappaB polymorphism is associated with heart function in patients with heart failure

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology
• Genetic Epidemiology

Background:

• Cardiac remodeling is a negative prognostic indicator in heart failure (HF).
• The transcription factor NFkB's role in cardiac remodeling is debated.
• A promoter polymorphism in the NFKB1 gene, linked to reduced activation, was previously associated with Dilated Cardiomyopathy.

Purpose of the Study:

• To investigate the association of the NFKB1 -94 insertion/deletion ATTG polymorphism with clinical and functional characteristics in HF patients.
• To evaluate the polymorphism's impact on disease onset and severity in different HF etiologies.

Main Methods:

• Genotyping of the NFKB1 -94 ATTG polymorphism in 493 HF patients and 916 general population controls.
• Comparison of allele and genotype frequencies between groups.
• Prospective follow-up of HF patients for mortality and disease onset, correlating with genotypes.

Main Results:

• No significant differences in genotype or allelic frequencies were observed between HF cases and controls.
• The ATTG1/ATTG1 genotype was associated with increased right and left ventricle diameters and lower ejection fraction (EF < 50%).
• ATTG1/ATTG1 carriers exhibited significantly earlier disease onset.

Conclusions:

• The NFKB1 -94 ATTG polymorphism is not associated with the occurrence of HF.
• Diminished NFKB1 activation via the ATTG1/ATTG1 genotype may modulate HF onset.
• This genotype might influence HF severity by exacerbating cardiac remodeling and functional decline.