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  • Title: Genetic factors associated with exercise performance in atmospheric hypoxia.
    Author: Hennis PJ, O'Doherty AF, Levett DZ, Grocott MP, Montgomery HM.
    Journal: Sports Med; 2015 May; 45(5):745-61. PubMed ID: 25682119.
    Abstract:
    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 ([Formula: see text]O2max) (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 median score achieved in the study quality analysis was 6 out of 10 for case-control studies, 8 out of 10 for cohort studies with a discrete outcome, 6 out of 9 for cohort studies with a continuous outcome, and 4.5 out of 8 for genetic admixture studies. CONCLUSION: The small number of articles identified in the current review and the limited number of polymorphisms studied in total highlights that the influence of genetic factors on exercise performance in hypoxia has not been studied in depth, which precludes firm conclusions being drawn. Support for the association between the ACE-I allele and improved high-altitude performance was the strongest, with three studies identifying a relationship. Analysis of study quality highlights the need for future studies in this field to improve the conduct and reporting of genetic association studies.
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