Abstract
BackgroundCardiac 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.MethodsA 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.ResultsWe 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.ConclusionThere 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.
Highlights
Cardiac remodeling is generally an adverse sign and is associated with heart failure (HF) progression
Cardiac remodeling is defined as alterations in left ventricular (LV) chamber mass, geometry and function, and is associated with heart failure (HF) progression[1]
Nuclear factor (NF) κB is a central integrator of stress response and cell survival pathways[4]
Summary
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. A promoter polymorphism associated with a lesser activation of the NFKB1 gene was 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. Cardiac remodeling is defined as alterations in left ventricular (LV) chamber mass, geometry and function, and is associated with heart failure (HF) progression[1]. The Rel/NFκB transcription factor is from a family of evolutionary conserved proteins that are all related through the highly conserved Rel homology binding domain. Transcription activation is dependent on subunit's dimerization. The p50 subunit (50 kDa) is encoded in humans by the gene NFKB1 and corresponds to the Nterminus of the cytoplasmic protein p105 (105 kDa)[9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
