title: HIF1A P582S gene association with endurance training responses in young women.
abstract: Sequence variations in the gene encoding the hypoxia-inducible factor-1alpha, HIF1A, have been associated with physiologic function and could be associated with exercise responses. In the HIF1A P582S gene polymorphism (C1772T; rs 11549465 C/T), a single nucleotide transition from C → T alters the codon sequence from the usual amino acid; proline (C-allele), to serine (T-allele). This polymorphism was examined for association with endurance training responses in 58 untrained young women who completed a 6-week laboratory-based endurance training programme. Participant groups were defined as CC homozygotes versus carriers of a T-allele (CC vs. CT genotypes). Adaptations were examined at the systemic-level, by measuring [Formula: see text] and the molecular-level by measuring enzymes determined from vastus lateralis (n = 20): 3-hydroacyl-CoA-dehydrogenase (HAD), which regulates mitochondrial fatty acid oxidation; cytochrome C oxidase (COX-1), a marker of mitochondrial density; and phosphofructokinase (PFK), a marker of glycolytic capacity. CT genotypes showed 45% higher training-induced gains in [Formula: see text] compared with CC genotypes (P < 0.05). At the molecular level, CT increased the ratios PFK/HAD and PFK/COX-1 (47 and 3%, respectively), while in the CC genotypes these ratios were decreased (-26 and -54%, respectively). In conclusion, the T-allele of HIF1A P582S was associated with greater gains in [Formula: see text] following endurance training in young women. In a sub-group we also provide preliminary evidence of differential muscle metabolic adaptations between genotypes.
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, John Dalton Building (room 216), Oxford Road, Manchester, M1 5GD, UK. j.s.mcphee@mmu.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: McPhee
authors.forename: J
authors.initials: J
authors.lastname: Perez-Schindler
authors.forename: H
authors.initials: H
authors.lastname: Degens
authors.forename: D
authors.initials: D
authors.lastname: Tomlinson
authors.forename: P
authors.initials: P
authors.lastname: Hennis
authors.forename: K
authors.initials: K
authors.lastname: Baar
authors.forename: A G
authors.initials: AG
authors.lastname: Williams
mesh_terms: D000367:Age Factors; D019943:Amino Acid Substitution; D005080:Exercise Test; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D010806:Physical Education and Training; D010807:Physical Endurance / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics; D012737:Sex Factors; D055815:Young Adult
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012694:Serine; D011392:Proline