Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia.
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SUBMITTER: Peng Y
PROVIDER: S-EPMC5400376 | biostudies-literature | 2017 Apr
REPOSITORIES: biostudies-literature
Publications
Down-Regulation of EPAS1 Transcription and Genetic Adaptation of Tibetans to High-Altitude Hypoxia.
Peng Yi Y Cui Chaoying C He Yaoxi Y Ouzhuluobu Zhang Hui H Yang Deying D Zhang Qu Q Bianbazhuoma Yang Lixin L He Yibo Y Xiang Kun K Zhang Xiaoming X Bhandari Sushil S Shi Peng P Yangla Dejiquzong Baimakangzhuo Duojizhuoma Pan Yongyue Y Cirenyangji Baimayangji Gonggalanzi Bai Caijuan C Bianba Basang Ciwangsangbu Xu Shuhua S Chen Hua H Liu Shiming S Wu Tianyi T Qi Xuebin X Su Bing B
Molecular biology and evolution 20170401 4
Tibetans are well adapted to the hypoxic environments at high altitude, yet the molecular mechanism of this adaptation remains elusive. We reported comprehensive genetic and functional analyses of EPAS1, a gene encoding hypoxia inducible factor 2α (HIF-2α) with the strongest signal of selection in previous genome-wide scans of Tibetans. We showed that the Tibetan-enriched EPAS1 variants down-regulate expression in human umbilical endothelial cells and placentas. Heterozygous EPAS1 knockout mice ...[more]
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2016-11-08 | GSE89635 | GEO
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Project description:Hypoxia inducible factors, including HIF1A and HIF2A, play central roles in response to high-altitude hypoxia and genetic variants of HIF1A or HIF2A were associated with high-altitude sickness or adaptation. However, it remains to determine whether they are associated with tolerance to different levels of high-altitude selection pressure among native Tibetans. We recruited 189 Tibetan subjects living at 2,700 meters (Low level of high altitude, LHA), 197 at 3,200 meters (Middle level of high altitude of high altitude, MHA), 249 at 3,700 meters (High level of high altitude, HHA) and 269 at 4,700 meters (Very high level of high altitude, VHA) and performed association analysis of twelve tSNPs (tagging SNPs) in HIF1A and HIF2A with high-altitude. We found (1) a increasing trend of HIF2A rs5621780-C(18.4%, 15.9%, 32.8% and 31.1%, respectively, in LHA, MHA, HHA and VHA)(P = 3.56E-9); (2) increasing trends of HIF2A rs6756667-A(68.7%, 73.4%, 79.9% and 89.6%), rs7589621- G(74.6%, 77.9%, 83.7%, and 92.1%) and rs1868092-A(64.1%, 67.3%, 75.1% and 84.4%) (P = 3.56E-9, 4.68E-16, 1.17E-13 and 7.09E-14, respectively); (3) a increasing trend of haplotype AG (68.7%, 73.1%, 79.9% and 89.6%) (P = 2.22E-7) which was constructed by rs6756667 and rs7589621; (4) a strong linear correlation between major alleles of rs6756667-A (R2 = 0.997, P = 0.002), rs7589621-G (R2 = 0.994, P = 0.003), rs1868092-A (R2 = 0.985, P = 0.008) and altitude by linear correlation test. The associations between HIF2A variants and different level of high altitude support that extremely high-altitude hypoxia challenge imposes selective effects on HIF2A variants among native Tibetans.
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