Factor (NF) kappa B polymorphism is associated with heart function in patients with heart failure

Autor(es)

Santos, Diogo G. B. ^[1] ; Resende, Marina F. ^[1] ; Mill, Jose G. ^[2] ; Mansur, Alfredo J. ^[3] ; Krieger, Jose E. ^[1] ; Pereira, Alexandre C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, Sao Paulo - Brazil

^[2] Univ Fed Espirito Santo, Dept Physiol, Vitoria - Brazil

^[3] Univ Sao Paulo, Sch Med, Heart Inst Incor, Dept Cardiol, Clin Div, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC MEDICAL GENETICS; v. 11, JUN 9 2010.
• Citações Web of Science: 27

Resumo

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 ATTG(1)/ATTG(1) 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 ATTG(1)/ATTG(1) more frequent in patients with EF lower than 50% (P = 0.01). Finally, we observed a significantly earlier disease onset in ATTG(1)/ATTG(1) 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 ATTG(1)/ATTG(1) 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. (AU)

• Processo FAPESP: 08/51652-0 - Investigação genética em pacientes com cardiomiopatia dilatada
• Beneficiário: Diogo Gonçalves Biagi dos Santos
• Modalidade de apoio: Bolsas no Brasil - Mestrado