Open Access Research article

ACTN3 R577X polymorphism and long-term survival in patients with chronic heart failure

Sabrina Bernardez-Pereira12, Paulo Caleb Junior Lima Santos1, Jose Eduardo Krieger1, Alfredo Jose Mansur1 and Alexandre Costa Pereira1*

Author Affiliations

1 Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP, Brazil

2 Fluminense Federal University, Rio de Janeiro, Brazil

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BMC Cardiovascular Disorders 2014, 14:90  doi:10.1186/1471-2261-14-90

Published: 24 July 2014



Previous studies have shown the occurrence of actinin-3 deficiency in the presence of the R577X polymorphism in the ACTN3 gene. Our hypothesis is that this deficiency, by interfering with the function of skeletal muscle fiber, can result in a worse prognosis in patients with chronic heart failure.


A prospective cohort study was conducted from 2002 to 2004. The eligibility criteria included diagnosis of chronic heart failure stage C from different etiologies. We excluded all patients with concomitant disease that could be related to poor prognosis. ACTN3 rs1815739 (R577X) polymorphism was detected by high resolution melting analysis. Survival curves were calculated with the Kaplan-Meier method and evaluated with the log-rank statistic. The relationship between the baseline variables and the composite end-point of all-cause death was assessed using a Cox proportional hazards survival model.


A total of 463 patients were included in this study. The frequency of the ACTN3 577X variant allele was 39.0%. The LVEF mean was 45.6 ± 18.7% and the most common etiology of this study was hypertensive. After a follow-up of five years, 239 (51.6%) patients met the pre-defined endpoint. Survival curves showed higher mortality in patients carrying RX or XX genotypes compared with patients carrying RR genotype (p = 0.01).


R577X polymorphism in the ACTN3 gene was independently associated with worse survival in patients with chronic heart failure. Further studies are necessary to ensure its use as a marker of prognosis for this syndrome.

ACTN3; R577X; Polymorphism; Heart failure