Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2 alpha) polymorphism lowers hemoglobin concentration in Tibetan highlanders
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10363947" target="_blank" >RIV/00216208:11110/17:10363947 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1007/s00109-017-1519-3" target="_blank" >http://dx.doi.org/10.1007/s00109-017-1519-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00109-017-1519-3" target="_blank" >10.1007/s00109-017-1519-3</a>
Alternative languages
Result language
angličtina
Original language name
Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2 alpha) polymorphism lowers hemoglobin concentration in Tibetan highlanders
Original language description
Tibetans have lived at high altitude for generations and are thought to be genetically adapted to hypoxic environments. Most are protected from hypoxia-induced polycythemia, and a haplotype of EPAS1, encoding hypoxia-inducible factor (HIF-2 alpha), has been associated with lower hemoglobin levels. We earlier reported a Tibetan-specific EGLN1 haplotype encoding PHD2 which abrogates HIF augmentation in hypoxia. We genotyped 347 Tibetan individuals from varying altitudes for both the Tibetan-specific EGLN1 haplotype and 10 candidate SNPs in the EPAS1 haplotype and correlated their association with hemoglobin levels. The effect of the EGLN1 haplotype on hemoglobin exhibited age dependency at low altitude, while at higher altitudes, it showed a trend to lower hemoglobin levels in the presence of the Tibetan-selected EPAS1 rs142764723 C/C allele. The observed gene-environment and gene-gene interactions and the moderate effect of the EGLN1 and EPAS1 haplotypes on hemoglobin indicate that other modifiers exist. It remains to be determined whether a blunting of erythropoiesis or other physiological consequences of HIF downregulation are the primary drivers of these genetic adaptations among Tibetans.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
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Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Molecular Medicine
ISSN
0946-2716
e-ISSN
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Volume of the periodical
95
Issue of the periodical within the volume
6
Country of publishing house
DE - GERMANY
Number of pages
6
Pages from-to
665-670
UT code for WoS article
000402017500010
EID of the result in the Scopus database
2-s2.0-85013640219