NDLI: Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Petousi, Nayia Croft, Quentin P. P. Cavalleri, Gianpiero L. Cheng, Hung-Yuan Formenti, Federico Ishida, Koji Lunn, Daniel McCormack, Mark Shianna, Kevin V. Talbot, Nick P. Ratcliffe, Peter J. Robbins, Peter A.
Spatial Coverage	Tibet China
Description	Author Affiliation: Petousi N ( Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom)
Abstract	Tibetan natives have lived on the Tibetan plateau (altitude â¼ 4,000 m) for at least 25,000 years, and as such they are adapted to life and reproduction in a hypoxic environment. Recent studies have identified two genetic loci, EGLN1 and EPAS1, that have undergone natural selection in Tibetans, and further demonstrated an association of EGLN1/EPAS1 genotype with hemoglobin concentration. Both genes encode major components of the hypoxia-inducible factor (HIF) transcriptional pathway, which coordinates an organism's response to hypoxia. Patients living at sea level with genetic disease of the HIF pathway have characteristic phenotypes at both the integrative-physiology and cellular level. We sought to test the hypothesis that natural selection to hypoxia within Tibetans results in related phenotypic differences. We compared Tibetans living at sea level with Han Chinese, who are Tibetans' most closely related major ethnic group. We found that Tibetans had a lower hemoglobin concentration, a higher pulmonary ventilation relative to metabolism, and blunted pulmonary vascular responses to both acute (minutes) and sustained (8 h) hypoxia. At the cellular level, the relative expression and hypoxic induction of HIF-regulated genes were significantly lower in peripheral blood lymphocytes from Tibetans compared with Han Chinese. Within the Tibetans, we found a significant correlation between both EPAS1 and EGLN1 genotype and the induction of erythropoietin by hypoxia. In conclusion, this study provides further evidence that Tibetans respond less vigorously to hypoxic challenge. This is evident at sea level and, at least in part, appears to arise from a hyporesponsive HIF transcriptional system.
File Format	HTM / HTML
ISSN	87507587
e-ISSN	15221601
DOI	10.1152/japplphysiol.00535.2013
Journal	Journal of Applied Physiology
Issue Number	7
Volume Number	116
Language	English
Publisher	American Physiological Society
Publisher Date	2014-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Physiology Acclimatization Asian Continental Ancestry Group Genetics Basic Helix-loop-helix Transcription Factors Hypoxia-inducible Factor-proline Dioxygenases Anoxia Selection, Genetic Metabolism Cells, Cultured Epidemiology Erythropoietin Blood Gene Expression Regulation Haplotypes Hemoglobins Ethnology Physiopathology Oxygen Phenotype Pulmonary Artery Pulmonary Ventilation Time Factors Transcription, Genetic Vasoconstriction Comparative Study Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Sports Science

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