Key result
The NFKB1 ATTG1/ATTG1 genotype was not associated with overall mortality or heart failure occurrence, but was significantly associated with earlier disease onset by 7 years and worse cardiac function.
Why the study?
Is the NFKB1 -94 insertion/deletion ATTG polymorphism associated with heart failure occurrence, cardiac remodeling, and disease severity?
Observational (n=1,409)
Single-blind
Yes
Is the NFKB1 -94 insertion/deletion ATTG polymorphism associated with heart failure occurrence, cardiac remodeling, and disease severity?
p-value: p=0.8
While the NFKB1 ATTG1/ATTG1 genotype is not associated with the occurrence of heart failure, it may modulate disease severity by promoting cardiac remodeling and accelerating disease onset.
BACKGROUND: Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression. NFkB, an important transcription factor involved in many cell survival pathways, has been implicated in the remodeling process, but its role in the heart is still controversial. Recently, a promoter polymorphism associated with a lesser activation of the NFKB1 gene was also associated with Dilated Cardiomyopathy. The purpose of this study was to evaluate the association of this polymorphism with clinical and functional characteristics of heart failure patients of different etiologies. METHODS: A total of 493 patients with HF and 916 individuals from a cohort of individuals from the general population were investigated. The NFKB1 -94 insertion/deletion ATTG polymorphism was genotyped by High Resolution Melt discrimination. Allele and genotype frequencies were compared between groups. In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotype groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the polymorphism were compared regarding disease onset and mortality incidence in HF patients. RESULTS: We did not find differences in genotype and allelic frequencies between cases and controls. Interestingly, we found an association between the ATTG1/ATTG1 genotype with right ventricle diameter (P = 0.001), left ventricle diastolic diameter (P = 0.04), and ejection fraction (EF) (P = 0.016), being the genotype ATTG1/ATTG1 more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG1/ATTG1 carriers. CONCLUSION: There is no genotype or allelic association between the studied polymorphism and the occurrence of HF in the tested population. However, our data suggest that a diminished activation of NFKB1, previously associated with the ATTG1/ATTG1 genotype, may act modulating on the onset of disease and, once the individual has HF, the genotype may modulate disease severity by increasing cardiac remodeling and function deterioration.
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Santos et al. (2010) conducted an observational in Heart failure (n=1,409). NFKB1 -94 insertion/deletion ATTG polymorphism vs. ATTG2/ATTG2 genotype was evaluated on Overall mortality (p=0.8). The NFKB1 ATTG1/ATTG1 genotype was not associated with overall mortality or heart failure occurrence, but was significantly associated with earlier disease onset by 7 years and worse cardiac function.
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