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


Autoria(s): Santos, Diogo GB; Resende, Marina F; Mill, José G; Mansur, Alfredo J; Krieger, José E; Pereira, Alexandre C
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

26/08/2013

26/08/2013

2010

Resumo

Abstract 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.

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo [Grant numbers 2008/51652-0, 2009/0952421-4].

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo .

Identificador

1471-2350

http://www.producao.usp.br/handle/BDPI/32853

10.1186/1471-2350-11-89

http://www.biomedcentral.com/1471-2350/11/89

Idioma(s)

eng

Relação

BMC Medical Genetics

Direitos

openAccess

Santos et al; licensee BioMed Central Ltd. - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Tipo

article

original article