PMID- 36244759
OWN - NLM
STAT- MEDLINE
DCOM- 20221018
LR  - 20221118
IS  - 1347-4715 (Electronic)
IS  - 1342-078X (Print)
IS  - 1342-078X (Linking)
VI  - 27
DP  - 2022
TI  - Genetic and immune changes in Tibetan high-altitude populations contribute to 
      biological adaptation to hypoxia.
PG  - 39
LID - 10.1265/ehpm.22-00040 [doi]
LID - 39
AB  - BACKGROUND: Tibetans have lived at very high altitudes for thousands of years, 
      and have a distinctive suite of physiological traits that enable them to tolerate 
      environmental hypoxia. Expanding awareness and knowledge of the differences in 
      hematology, hypoxia-associated genes, immune system of people living at different 
      altitudes and from different ethnic groups may provide evidence for the 
      prevention of mountain sickness. METHOD: Ninety-five Han people at mid-altitude, 
      ninety-five Tibetan people at high-altitude and ninety-eight Han people at 
      high-altitude were recruited. Red blood cell parameters, immune cells, the 
      contents of cytokines, hypoxia-associated gene single nucleotide polymorphisms 
      (SNPs) were measured. RESULTS: The values of Hematocrit (HCT), Mean cell volume 
      (MCV) and Mean cell hemoglobin (MCH) in red blood cell, immune cell CD19(+) B 
      cell number, the levels of cytokines Erb-B2 receptor tyrosine kinase 3 (ErbB3) 
      and Tumor necrosis factor receptor II (TNF-RII) and the levels of 
      hypoxia-associated factors Hypoxia inducible factor-1alpha (HIF-1alpha), Hypoxia 
      inducible factor-2alpha (HIF-2alpha) and HIF prolyl 4-hydroxylase 2 (PHD2) were 
      decreased, while the frequencies of SNPs in twenty-six Endothelial PAS domain 
      protein 1 (EPAS1) and Egl-9 family hypoxia inducible factor 1 (EGLN1) were 
      increased in Tibetan people at high-altitude compared with that of Han peoples at 
      high-altitude. Furthermore, compared with mid-altitude individuals, high-altitude 
      individuals showed lower blood cell parameters including Hemoglobin concentration 
      (HGB), HCT, MCV and MCH, higher Mean cell hemoglobin concentration (MCHC), lower 
      immune cells including CD19(+) B cells, CD4(+) T cells and CD4/CD8 ratio, higher 
      immune cells containing CD8(+) T cells and CD16/56NK cells, decreased Growth 
      regulated oncogene alpha (GROa), Macrophage inflammatory protein 1 beta (MIP-1b), 
      Interleukin-8 (IL-8), and increased Thrombomodulin, downregulated 
      hypoxia-associated factors including HIF1alpha, HIF2alpha and PHD2, and higher frequency 
      of EGLN1 rs2275279. CONCLUSIONS: These results indicated that biological adaption 
      to hypoxia at high altitude might have been mediated by changes in immune cells, 
      cytokines, and hypoxia-associated genes during the evolutionary history of 
      Tibetan populations. Furthermore, different responses to high altitude were 
      observed in different ethnic groups, which may provide a useful knowledge to 
      improve the protection of high-altitude populations from mountain sickness.
FAU - Bai, Jun
AU  - Bai J
AD  - Institute of Hematology, Lanzhou University Second Hospital.
AD  - Gansu Key Laboratory of Hematology.
FAU - Li, Lijuan
AU  - Li L
AD  - Institute of Hematology, Lanzhou University Second Hospital.
AD  - Gansu Key Laboratory of Hematology.
FAU - Li, Yanhong
AU  - Li Y
AD  - Institute of Hematology, Lanzhou University Second Hospital.
AD  - Gansu Key Laboratory of Hematology.
FAU - Zhang, Liansheng
AU  - Zhang L
AD  - Institute of Hematology, Lanzhou University Second Hospital.
AD  - Gansu Key Laboratory of Hematology.
AD  - Dingxi People's Hospital.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Environ Health Prev Med
JT  - Environmental health and preventive medicine
JID - 9609642
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Hemoglobins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Interleukin-8)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Thrombomodulin)
RN  - EC 1.14.11.29 (Hypoxia-Inducible Factor-Proline Dioxygenases)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adaptation, Biological
MH  - *Altitude
MH  - *Altitude Sickness/genetics
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Chemokine CCL4/genetics
MH  - Hemoglobins/analysis
MH  - Humans
MH  - Hypoxia/genetics/metabolism
MH  - Hypoxia-Inducible Factor 1/genetics
MH  - Hypoxia-Inducible Factor-Proline Dioxygenases/genetics/metabolism
MH  - Interleukin-8/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Receptor, ErbB-2/genetics
MH  - Receptors, Tumor Necrosis Factor, Type II/genetics
MH  - Thrombomodulin/genetics
MH  - Tibet
PMC - PMC9640738
OTO - NOTNLM
OT  - Genetics
OT  - High altitude
OT  - Hypoxia
OT  - Immune
OT  - Tibetan
COIS- The authors declare no competing interests.
EDAT- 2022/10/17 06:00
MHDA- 2022/10/19 06:00
PMCR- 2022/10/15
CRDT- 2022/10/16 21:23
PHST- 2022/10/16 21:23 [entrez]
PHST- 2022/10/17 06:00 [pubmed]
PHST- 2022/10/19 06:00 [medline]
PHST- 2022/10/15 00:00 [pmc-release]
AID - 22-00040 [pii]
AID - 10.1265/ehpm.22-00040 [doi]
PST - ppublish
SO  - Environ Health Prev Med. 2022;27:39. doi: 10.1265/ehpm.22-00040.