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Eur J Appl Physiol. 2011 Sep;111(9):2339-47. doi: 10.1007/s00421-011-1869-4. Epub 2011 Feb 23.

HIF1A P582S gene association with endurance training responses in young women.

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Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, John Dalton Building (room 216), Oxford Road, Manchester, M1 5GD, UK.


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.

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