title: The ACTN3 R577X Polymorphism Is Associated with Cardiometabolic Fitness in Healthy Young Adults.
abstract: Homozygosity for a premature stop codon (X) in the ACTN3 "sprinter" gene is common in humans despite the fact that it reduces muscle size, strength and power. Because of the close relationship between skeletal muscle function and cardiometabolic health we examined the influence of ACTN3 R577X polymorphism over cardiovascular and metabolic characteristics of young adults (n = 98 males, n = 102 females; 23 ± 4.2 years) from our Assessing Inherent Markers for Metabolic syndrome in the Young (AIMMY) study. Both males and females with the RR vs XX genotype achieved higher mean VO2 peak scores (47.8 ± 1.5 vs 43.2 ±1.8 ml/O2/min, p = 0.002) and exhibited higher resting systolic (115 ± 2 vs 105 ± mmHg, p = 0.027) and diastolic (69 ± 3 vs 59 ± 3 mmHg, p = 0.005) blood pressure suggesting a role for ACTN3 in the maintenance of vascular tone. We subsequently identified the expression of alpha-actinin 3 protein in pulmonary artery smooth muscle, which may explain the genotype-specific differences in cardiovascular adaptation to acute exercise. In addition, we utilized targeted serum metabolomics to distinguish between RR and XX genotypes, suggesting an additional role for the ACTN3 R577X polymorphism in human metabolism. Taken together, these results identify significant cardiometabolic effects associated with possessing one or more functional copies of the ACTN3 gene.
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Deschamps
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Connors
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Klein
authors.affiliation: Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Johnsen
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada; Faculty of Kinesiology, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Jane
authors.initials: J
authors.lastname: Shearer
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
authors.affiliation: Children's National Medical Center, 111 Michigan Ave NW, Washington DC, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Devaney
authors.affiliation: Children's National Medical Center, 111 Michigan Ave NW, Washington DC, United States of America.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Children's National Medical Center, 111 Michigan Ave NW, Washington DC, United States of America.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Many
authors.affiliation: Children's National Medical Center, 111 Michigan Ave NW, Washington DC, United States of America.
authors.forename: Whitney
authors.initials: W
authors.lastname: Barfield
authors.affiliation: Children's National Medical Center, 111 Michigan Ave NW, Washington DC, United States of America.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.affiliation: Duke University, 304 Research Drive, Durham, NC, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, 2500 University Drive, Calgary, Alberta, T2N 1N4, Canada.
authors.forename: Dustin S
authors.initials: DS
authors.lastname: Hittel
mesh_terms: D000185:Actinin / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D054874:Athletic Performance / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology*; D010807:Physical Endurance / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011651:Pulmonary Artery / Q000502:physiology; D012129:Respiratory Function Tests
chemical_list: C118456:ACTN3 protein, human; D000185:Actinin