Genetic and immune changes in Tibetan high-altitude populations contribute to biological adaptation to hypoxia.

Abstract

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-1α (HIF-1α), Hypoxia inducible factor-2α (HIF-2α) 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 HIF1α, HIF2α 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.

• Authors: Jun Bai, Lijuan Li, Yanhong Li, Liansheng Zhang
• Journal: Environmental health and preventive medicine (Environ Health Prev Med) Vol. 27 Pg. 39 ( 2022) ISSN: 1347-4715 [Electronic] Japan
• PMID: 36244759 (Publication Type: Journal Article)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• Chemokine CCL4
• Hemoglobins
• Hypoxia-Inducible Factor 1
• Interleukin-8
• Receptors, Tumor Necrosis Factor, Type II
• Thrombomodulin
• Hypoxia-Inducible Factor-Proline Dioxygenases
• Receptor, ErbB-2

Topics

• Adaptation, Biological
• Altitude
• Altitude Sickness (genetics)
• Basic Helix-Loop-Helix Transcription Factors (genetics)
• CD8-Positive T-Lymphocytes (metabolism)
• Chemokine CCL4 (genetics)
• Hemoglobins (analysis)
• Humans
• Hypoxia (genetics, metabolism)
• Hypoxia-Inducible Factor 1 (genetics)
• Hypoxia-Inducible Factor-Proline Dioxygenases (genetics, metabolism)
• Interleukin-8 (genetics)
• Polymorphism, Single Nucleotide
• Receptor, ErbB-2 (genetics)
• Receptors, Tumor Necrosis Factor, Type II (genetics)
• Thrombomodulin (genetics)
• Tibet