A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1 alpha (HIF1A) gene in elite endurance athletes

作者：Doering Frank; Onur Simone; Fischer Alexandra; Boulay Marcel R; Perusse Louis; Rankinen Tuomo; Rauramaa Rainer; Wolfarth Bernd; Bouchard Claude

来源：Journal of Applied Physiology, 2010, 108(6): 1497-1500.

DOI：10.1152/japplphysiol.01165.2009

• single nucleotide polymorphism
• exercise genetics

Doring F, Onur S, Fischer A, Boulay MR, Perusse L, Rankinen T, Rauramaa R, Wolfarth B, Bouchard C. A common haplotype and the Pro582Ser polymorphism of the hypoxia-inducible factor-1 alpha (HIF1A) gene in elite endurance athletes. J Appl Physiol 108: 1497-1500, 2010. First published March 18, 2010; doi:10.1152/japplphysiol.01165.2009.-Hypoxia-inducible factor-1 alpha (HIF1A) is a transcription factor regulating several genes in response to hypoxic stimuli. HIF1A target genes code for proteins involved in oxygen transport, glycolytic enzymes, and glucose transporters. We investigated whether single-nucleotide polymorphisms and haplotypes in the HIF1A gene are associated with endurance performance in the Genathlete cohort, which includes 316 Caucasian male elite endurance athletes (EEA) with a maximal oxygen uptake of 79.0 +/- 3.5 ml.kg(-1).min(-1) (mean +/- SD) and 304 Caucasian male sedentary controls with a maximal oxygen uptake of 40.1 +/- 7.0 ml.kg(-1).min(-1). Six single-nucleotide polymorphisms (rs1951795, rs11158358, rs2301113, rs11549465, rs115494657, rs17099207) were genotyped with the TaqMan system. We found a nominal significant tendency for a difference between the two groups for HIF1A Pro582Ser (rs11549465) genotype distributions (P chi(2) = 0.017). Homozygotes of the Pro genotype were slightly more frequent in athletes than in controls (84 vs. 75%). Compared with Ser carriers, the odds ratio (OR) of being an EEA in Pro/Pro homozygotes was 1.77 [95% confidence interval (CI): 1.18-2.67, P = 0.006] compared with the other genotypes. A common HIF1A haplotype (frequency: 15%), including the rs11549465 Pro allele and the minor A allele of rs17099207 in the 3 ' flanking region of the gene, showed a significant association with EEA status (OR: 2.37, 95% CI: 1.21-4.66, P = 0.012), whereas the most prevalent haplotype (frequency: 59%) comprising the rs11549465 Pro allele and the major G allele of rs1709920 showed no association with EEA status (OR: 0.93, 95% CI: 0.58-1.50, P = 0.769). We found preliminary evidence that the HIF1A Pro582Ser polymorphism and a common haplotype of the HIF1A gene may be associated with EEA status in Caucasian men.

• 出版日期2010-6