HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans.
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 lev...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4569405?pdf=render |
| _version_ | 1818275155964592128 |
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| author | Zhuoma Basang Boyang Wang Lei Li La Yang Lan Liu Chaoying Cui Gongga Lanzi Nima Yuzhen Ji Duo Hongxiang Zheng Yi Wang Shuhua Xu Li Jin Xiaofeng Wang |
| author_facet | Zhuoma Basang Boyang Wang Lei Li La Yang Lan Liu Chaoying Cui Gongga Lanzi Nima Yuzhen Ji Duo Hongxiang Zheng Yi Wang Shuhua Xu Li Jin Xiaofeng Wang |
| author_sort | Zhuoma Basang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T22:25:16Z |
| format | Article |
| id | doaj.art-75a8d0942f624539835724f43db97374 |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T22:25:16Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-75a8d0942f624539835724f43db973742022-12-22T00:09:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013795610.1371/journal.pone.0137956HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans.Zhuoma BasangBoyang WangLei LiLa YangLan LiuChaoying CuiGongga LanziNima YuzhenJi DuoHongxiang ZhengYi WangShuhua XuLi JinXiaofeng WangHypoxia 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.http://europepmc.org/articles/PMC4569405?pdf=render |
| spellingShingle | Zhuoma Basang Boyang Wang Lei Li La Yang Lan Liu Chaoying Cui Gongga Lanzi Nima Yuzhen Ji Duo Hongxiang Zheng Yi Wang Shuhua Xu Li Jin Xiaofeng Wang HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. PLoS ONE |
| title | HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. |
| title_full | HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. |
| title_fullStr | HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. |
| title_full_unstemmed | HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. |
| title_short | HIF2A Variants Were Associated with Different Levels of High-Altitude Hypoxia among Native Tibetans. |
| title_sort | hif2a variants were associated with different levels of high altitude hypoxia among native tibetans |
| url | http://europepmc.org/articles/PMC4569405?pdf=render |
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