Tashi, Tsewang and Scott Reading, N. and Wuren, Tanna and Zhang, Xu and Moore, Lorna G. and Hu, Hao and Tang, Feng and Shestakova, Anna and Lorenzo, Felipe and Burjanivova, Tatiana and Koul, Parvaiz and Guchhait, Prasenjit and Wittwer, Carl T. and Julian, Colleen G. and Shah, Binal and Huff, Chad D. and Gordeuk, Victor R. and Prchal, Josef T. and Ge, RiLi (2017) Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphism lowers hemoglobin concentration in Tibetan highlanders. Journal of Molecular Medicine, 95 (6). pp. 665-670. ISSN 0946-2716

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Abstract

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-2α), 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.

Item Type:	Article
Subjects:	Biomedical Science Biochemical and Biophysical Sciences
Depositing User:	Dr Vengadesan Krishnan
Date Deposited:	11 Mar 2018 06:43
Last Modified:	11 Mar 2018 06:43
URI:	http://rcb.sciencecentral.in/id/eprint/145

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