Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

Authors: Fiuza-Luces C; Ruiz JR; Rodríguez-Romo G; Santiago C; Gómez-Gallego F; Yvert T; Cano-Nieto A; Garatachea N; Morán M; Lucia A

Abstract: Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching >/=100 years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein alpha-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100-108 years), young healthy controls (n = 283, 67 females, 216 males; 21+/-2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (alpha-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain 'survival' advantage brought about by alpha-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.

Keywords: Actinin/*genetics; Adult; Aged, 80 and over; *Alleles; Amino Acid Substitution/*genetics; Cohort Studies; Female; Genotype; Humans; Male; Physical Endurance/*genetics; Polymorphism, Single Nucleotide/*genetics; Young Adult
Journal: PloS one
Volume: 6
Issue: 3
Pages: e17558
Date: March 17, 2011
PMID: 21407828
Select reference article to upload


Citation:

Fiuza-Luces C, Ruiz JR, Rodríguez-Romo G, Santiago C, Gómez-Gallego F, Yvert T, Cano-Nieto A, Garatachea N, Morán M, Lucia A (2011) Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism. PloS one 6: e17558.


Longevity Variant Associations (p-value):
  • rs1815739 (0.1)

  • Update (Admin) | Auto-Update

    Comment on This Data Unit