title: Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.
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 α-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 (α-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 α-actinin-3 deficiency and the 'endurance'/oxidative muscle phenotype that is commonly associated with this condition.
authors.affiliation: Universidad Europea de Madrid, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fiuza-Luces
authors.forename: Jonatan R
authors.initials: JR
authors.lastname: Ruiz
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodríguez-Romo
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.forename: Félix
authors.initials: F
authors.lastname: Gómez-Gallego
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.forename: Amalia
authors.initials: A
authors.lastname: Cano-Nieto
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.forename: María
authors.initials: M
authors.lastname: Morán
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000185:Actinin / Q000235:genetics*; D000328:Adult; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010807:Physical Endurance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: C118456:ACTN3 protein, human; D000185:Actinin