Physiol. Genomics Journal of Applied Physiology
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Physiol. Genomics (July 15, 2003). doi:10.1152/physiolgenomics.00061.2003
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Submitted on April 9, 2003
Accepted on July 7, 2003

Sequence variation in hypoxia-inducible factor 1{alpha} (HIF1A): Association with maximal oxygen consumption

Steven J Prior1, James M Hagberg1, Dana A Phares1, Michael D Brown1, Liane Fairfull2, Robert E Ferrell2, and Stephen M Roth3*

1 Department of Kinesiology, University of Maryland, College Park, MD, USA
2 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
3 Department of Kinesiology, University of Maryland, College Park, MD, USA; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA

* To whom correspondence should be addressed. E-mail: sroth1{at}umd.edu.

Hypoxia-inducible factor 1 (HIF1) is a DNA transcription factor composed of two subunits, one of which is regulated by hypoxia (HIF1{alpha}, encoded by HIF1A). Genes regulated by HIF1 are involved in the processes of angiogenesis, erythropoiesis, and metabolism, making HIF1A a candidate gene in establishing maximal oxygen consumption (Vo2max) before and after aerobic exercise training. The purpose of the present study was to screen HIF1A for sequence variation and determine if such variation is associated with Vo2max before and after aerobic exercise training. A total of 233 Caucasian and African-American subjects were available for screening of HIF1A and determination of allele frequencies, with 155 of those subjects used to study Vo2max in relation to identified variants. We measured Vo2max before and after 24 weeks of aerobic exercise training. Screening revealed several rare and common polymorphisms in HIF1A with race-specific allele frequencies. African-Americans with AT or TT genotype at the A-2500T locus exhibited significantly lower baseline Vo2max compared to those of AA genotype (21.9±0.99 vs. 25.1±1.0, p=0.03). An age by P582S (C/T) genotype interaction was observed in Caucasian subjects, such that those of CT or TT genotype exhibited significantly lower change in Vo2max after training than those of CC genotype when compared at ages 65 and 60, but not at age 55. No other significant differences were noted among genotype groups at the A-2500T, P582S, or T+140C sites. Based on these findings, we conclude that HIF1A sequence variation is associated with Vo2max before and after aerobic exercise training in older humans.




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