Genetic Factors Associated with Exercise Performance in Atmospheric Hypoxia

• Published in: Sports medicine (Auckland) 2015-05, Vol.45 (5), p.745-761
• Main Authors: Hennis, Philip J., O’Doherty, Alasdair F., Levett, Denny Z. H., Grocott, Michael P. W., Montgomery, Hugh M.
• Format: Article
• Language: English
• Subjects: Actinin - genetics; Altitude Sickness - genetics; Altitude Sickness - physiopathology; AMP Deaminase - genetics; Athletic Performance - physiology; Exercise; Exercise - physiology; Genetic Variation; Genotype; Humans; Hypoxia; INDEL Mutation; Medicine; Medicine & Public Health; Methods; Mountain climbing; Oxygen Consumption - physiology; Peptidyl-Dipeptidase A - genetics; Sea level; Sports Medicine; Studies; Systematic Review
• ISSN: 0112-1642; 1179-2035
• DOI: 10.1007/s40279-015-0309-8

Background and Objective ‘Natural selection’ has been shown to have enriched the genomes of high-altitude native populations with genetic variants of advantage in this hostile hypoxic environment. In lowlanders who ascend to altitude, genetic factors may also contribute to the substantial interindividual variation in exercise performance noted at altitude. We performed a systematic literature review to identify genetic variants of possible influence on human hypoxic exercise performance, commenting on the strength of any identified associations. Criteria for considering studies for this review All studies of the association of genetic factors with human hypoxic exercise performance, whether at sea level using ‘nitrogen dilution of oxygen’ (normobaric hypoxia), or at altitude or in low-pressure chambers (field or chamber hypobaric hypoxia, respectively) were sought for review. Search strategy for identification of studies Two electronic databases were searched (Ovid MEDLINE, Embase) up to 31 January 2014. We also searched the reference lists of relevant articles for eligible studies. All studies published in English were included, as were studies in any language for which the abstract was available in English. Data collection and analysis Studies were selected and data extracted independently by two reviewers. Differences regarding study inclusion were resolved through discussion. The quality of each study was assessed using a scoring system based on published guidelines for conducting and reporting genetic association studies. Results A total of 11 studies met all inclusion criteria and were included in the review. Subject numbers ranged from 20 to 1,931 and consisted of healthy individuals in all cases. The maximum altitude of exposure ranged from 2,690 to 8,848 m. The exercise performance phenotypes assessed were mountaineering performance ( n  = 5), running performance ( n  = 2), and maximum oxygen consumption ( V ˙ O 2 max) ( n  = 4). In total, 13 genetic polymorphisms were studied, four of which were associated with hypoxic exercise performance. The adenosine monophosphate deaminase (AMPD1) C34T (rs17602729), beta2-adrenergic receptor (ADRB2) Gly16Arg single nucleotide polymorphism (SNP) (rs1042713), and androgen receptor CAG repeat polymorphisms were associated with altitude performance in one study, and the angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) (rs4646994) polymorphism was associated with performance in three studies. The me