ACTN3R577X polymorphism and long-term survival in patients with chronic heart failure

Abstract

BackgroundPrevious 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.MethodsA 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.ResultsA 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).ConclusionR577X 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.

Polymorphisms in<i> ACE</i> and <i>ACTN3</i> Genes and Blood Pressure Response to Acute Exercise in Elite Male Athletes from Serbia

“…Also, the latest scientific data describe a role of this polymorphism, not only in all-cause mortality in humans, but also with increased survival time in patients with chronic heart failure, suggesting a potential extra-sarcomeric role for α-actinin-3 (Bernardez-Pereira et al 2014). Observed widespread expression of ACTN3, not only in skeletal muscles, but in many other tissues, and especially in pulmonary artery, may be responsible for changes in vascular myogenic tone, and consequently could explain observed differences in BP in athletes in different sports, as well as different vascular response in various types of physical activity (Kim et al 2014).…”

The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults

“…While our findings need to be validated in situ it is conceivable that changes vascular myogenic tone in response to alpha-actinin-3 deficiency could explain differences in resting blood pressure as well as altered vascular recruitment in response to an acute exercise stress test [ 39 , 40 ]. Furthermore, it has not escaped our attention that the expression (or lack thereof) of alpha-actinin 3 in pulmonary artery could explain the gene-stratified differences in survival of patients with chronic heart failure [ 14 ]. Regardless of the underlying mechanism, these novel associations have clinical relevance given the wide spread use of the Bruce protocol to assess cardiac function and aerobic capacity [ 35 ].…”

“…Recently a number of studies have described a role for ACTN3 R577X in the aging process and all-cause mortality in humans [ 12 , 13 ]. Notably, the R577 allele has been associated with increased survival times in patients with chronic heart failure [ 14 ] as well as increased bone mineral density/decreased fracture risk [ 15 ] suggesting an extra-sarcomeric role for α-actinin-3. While much of the research on ACTN3 has focused on skeletal muscle phenotypes related to power/strength driven sports [ 16 ] there have been relatively few studies identifying associations with specific components of cardiovascular and metabolic fitness [ 12 , 17 ].…”

Is evolutionary loss our gain? The role of ACTN3 p.Arg577Ter (R577X) genotype in athletic performance, ageing, and disease

“…The ACTN3 X allele has now been linked with increased likelihood of developing inflammatory myopathies (Sandoval‐Garcia et al., ) and earlier onset of Pompe disease (De Filippi et al., ). ACTN3 genotype has also been correlated with survival in patients with congestive heart failure, where patients with the X allele have 1.72 times higher mortality than their peers with ACTN3 577RR genotype ( P = 0.01) (Bernardez‐Pereira, Santos, Krieger, Mansur, & Pereira, ). These observations suggest that ACTN3 genotype may play a role in modifying disease severity and age of onset for a number of clinical conditions.…”