Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, John Dalton Building (room 216), Oxford Road, Manchester, M1 5GD, UK.
Eur J Appl Physiol. 2011 Sep;111(9):2339-47. doi: 10.1007/s00421-011-1869-4. Epub 2011 Feb 23.
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.
基因编码的缺氧诱导因子-1α（HIF1A）序列变异与生理功能有关，也可能与运动反应有关。在 HIF1A P582S 基因多态性（C1772T；rs11549465C/T）中，一个从 C 到 T 的单一核苷酸转换改变了密码子序列，使通常的氨基酸脯氨酸（C-等位基因）变为丝氨酸（T-等位基因）。这项多态性研究了 58 名未经训练的年轻女性在完成 6 周基于实验室的耐力训练计划后的耐力训练反应。参与者群体被定义为 CC 纯合子与携带 T 等位基因的个体（CC 与 CT 基因型）。通过测量[Formula: see text]来评估全身适应，通过测量从股外侧肌中测定的酶来评估分子水平：3-羟酰基辅酶 A 脱氢酶（HAD），调节线粒体脂肪酸氧化；细胞色素 C 氧化酶（COX-1），线粒体密度的标志物；和磷酸果糖激酶（PFK），糖酵解能力的标志物。CT 基因型与 CC 基因型相比，训练诱导的[Formula: see text]增加了 45%（P<0.05）。在分子水平上，CT 增加了 PFK/HAD 和 PFK/COX-1 的比值（分别为 47%和 3%），而在 CC 基因型中，这些比值分别降低（分别为-26%和-54%）。总之，HIF1A P582S 的 T 等位基因与年轻女性进行耐力训练后[Formula: see text]的增加有关。在一个亚组中，我们还提供了基因型之间肌肉代谢适应差异的初步证据。
