eprintid: 10045374 rev_number: 33 eprint_status: archive userid: 608 dir: disk0/10/04/53/74 datestamp: 2018-03-15 17:48:12 lastmod: 2021-12-13 02:28:50 status_changed: 2018-03-15 17:48:12 type: article metadata_visibility: show creators_name: Hennis, PJ creators_name: O'Doherty, AF creators_name: Levett, DZH creators_name: Grocott, MPW creators_name: Montgomery, HM title: Genetic Factors Associated with Exercise Performance in Atmospheric Hypoxia ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: C10 divisions: D17 divisions: G94 divisions: D13 keywords: Exercise Performance, Genetic Association Study, Hypoxic Exposure, Normobaric Hypoxia, AMPD note: Copyright © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. 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 ( V˙V˙ 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. date: 2015-05-01 date_type: published publisher: ADIS INT LTD official_url: http://doi.org/10.1007/s40279-015-0309-8 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type: review verified: verified_manual elements_id: 1016055 doi: 10.1007/s40279-015-0309-8 lyricists_name: Grocott, Michael lyricists_name: Levett, Denny lyricists_name: Montgomery, Hugh lyricists_id: MGROC26 lyricists_id: DZHLE97 lyricists_id: HEMON01 actors_name: Waragoda Vitharana, Nimal actors_id: NWARR44 actors_role: owner full_text_status: public publication: Sports Medicine volume: 45 number: 5 pagerange: 727-743 pages: 17 issn: 1179-2035 citation: Hennis, PJ; O'Doherty, AF; Levett, DZH; Grocott, MPW; Montgomery, HM; (2015) Genetic Factors Associated with Exercise Performance in Atmospheric Hypoxia. [Review]. Sports Medicine , 45 (5) pp. 727-743. 10.1007/s40279-015-0309-8 <https://doi.org/10.1007/s40279-015-0309-8>. Green open access document_url: https://discovery-pp.ucl.ac.uk/id/eprint/10045374/1/Genetic%20factors%20associated%20with%20exercise%20performance%20in%20atmospheric%20hypoxia.pdf