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Sequence variation in hypoxia-inducible factor 1 (HIF1A): association with maximal oxygen consumption

¹ Department of Kinesiology, University of Maryland, College Park, Maryland 20742
² Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Hypoxia-inducible factor 1 (HIF1) is a DNA transcription factor composed of two subunits, one of which is regulated by hypoxia (HIF1, 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 (V^·O_{2 max}) before and after aerobic exercise training. The purpose of the present study was to screen HIF1A for sequence variation and determine whether such variation is associated with V^·O_{2 max} 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 V^·O_{2 max} in relation to identified variants. We measured V^·O_{2 max} before and after 24 wk 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 V^·O_{2 max} compared with 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 V^·O_{2 max} after training than those of CC genotype when compared at ages 65 and 60 yr, but not at age 55 yr. 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 V^·O_{2 max} before and after aerobic exercise training in older humans.

exercise; sex; genetics; polymorphism; race

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