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PLoS By Category | Recent PLoS Articles
Geriatrics

Are ‘Endurance’ Alleles ‘Survival’ Alleles? Insights from the ACTN3 R577X Polymorphism
Published: Thursday, March 03, 2011
Author: Carmen Fiuza-Luces et al.

by Carmen Fiuza-Luces, Jonatan R. Ruiz, Gabriel Rodríguez-Romo, Catalina Santiago, Félix Gómez-Gallego, Thomas Yvert, Amalia Cano-Nieto, Nuria Garatachea, María Morán, Alejandro Lucia

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 =100years 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 a-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 (a-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 a-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.
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