Associations between HIF1A gene sequence variation and cardiorespiratory fitness: The CARDIA Fitness Study

Hypoxia inducible factor 1 alpha (HIF1A) is a transcription factor that regulates expression of several genes in response to hypoxia. Sequence variation in the HIF1A gene (rs11549465) has previously been associated with VO 2max training response and elite endurance athlete status in Caucasians. Purpose of our study was to examine the association of DNA sequence variants in the HIF1A gene locus and cardiorespiratory (CR) fitness level measured at baseline of the CARDIA Fitness Study. The study population consisted of 4258 (2129 African‐Americans, 2162 Caucasians) young adults with mean age of 24.9 (SD 3.6) years. CR fitness was measured as treadmill time (TMT) on a graded exercise test. The associations between TMT and HIF1A SNPs (13 for African‐Americans, 6 for Caucasians; minor allele frequency > 4%) were analyzed using general linear models with adjustments for age, sex, and body weight. In Caucasians, SNP rs1957757 was significantly associated with TMT (nominal p=0.001, Bonferroni‐corrected p=0.006): the T/T homozygotes (n=21) had 1.3 and 1.5 minutes longer TMT than the C/T heterozygotes (n=316) and the C/C homozygotes (n=1624), respectively. No other SNP was significantly associated with TMT in Caucasians. None of the SNPs were associated with TMT in African‐Americans. Our data suggests that DNA sequence variation in the HIF1A gene locus is associated with treadmill time in Caucasian young adults.