Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor system and blunted physiological responses to hypoxia.
J Appl Physiol (1985)
; 116(7): 893-904, 2014 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-24030663
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Selection, Genetic
/
Asian People
/
Basic Helix-Loop-Helix Transcription Factors
/
Altitude
/
Hypoxia-Inducible Factor-Proline Dioxygenases
/
Acclimatization
/
Hypoxia
Type of study:
Prognostic_studies
Limits:
Adult
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
J Appl Physiol (1985)
Journal subject:
FISIOLOGIA
Year:
2014
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA