International Journal of Hematology

, Volume 96, Issue 2, pp 200–213 | Cite as

AKT3, ANGPTL4, eNOS3, and VEGFA associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau

  • Norman E. Buroker
  • Xue-Han Ning
  • Zhao-Nian Zhou
  • Kui Li
  • Wei-Jun Cen
  • Xiu-Feng Wu
  • Wei-Zhong Zhu
  • C. Ronald Scott
  • Shi-Han Chen
Original Article

Abstract

Mountain sickness (MS) occurs among humans visiting or inhabiting high altitude environments. We conducted genetic analyses of the AKT3, ANGPTL4, eNOS3 and VEGFA genes in lowland (Han) and highland (Tibetan) Chinese. Ten single nucleotide polymorphisms (SNPs) were evaluated in Han and Tibetan patients with acute (A) and chronic (C) MS. We compared 74 patients with AMS to 79 Han unaffected with MS, as well as 48 CMS patients to 31 unaffected Tibetans. The ten SNPs studied are AKT3 (rs4590656, rs2291409), ANGPTL4 (rs1044250), eNOS3 (rs1007311, rs1799983) and VEGFA (rs79469752, rs13207351, rs28357093, rs1570360, rs3025039). Direct sequencing was used to identify individual genotypes for these SNPs. Hemoglobin (Hb), hematocrit (Hct), and red blood cell count (RBC) were found to be significantly associated with the AKT3 SNP (rs4590656), Hb was found to be associated with the eNOS3 SNP (rs1007311), and RBC was found to be significantly associated with the VEGFA SNP (rs1570360) in Tibetan patients with CMS. CMS patients were found to diverge significantly for both eNOS3 SNPs as measured by genetic distance (0.042, 0.047) and for the VEGFA SNP (rs28357093) with a genetic distance of 0.078 compared to their Tibetan control group. Heart rate (HR) was found to be significantly associated with the eNOS3 SNP (rs1799983) and arterial oxygen saturation of hemoglobin (SaO2) was found to be significantly associated with the VEGFA SNPs (rs13207351, rs1570360) in Han patients with AMS. The Han and Tibetan control groups were found to diverge significantly for the ANGPTL4 SNP and VEGFA SNP (rs28357093), as measured by genetic distances of 0.049 and 0.073, respectively. Seven of the SNPs from non-coding regions are found in the transcriptional factor response elements and their possible role in gene regulation was evaluated with regard to MS. AMS and CMS were found to be significantly associated with the four genes compared to their Han and Tibetan control groups, respectively, indicating that these nucleotide alterations have a physiological effect for the development of high altitude sickness.

Keywords

Acute and chronic mountain sickness AKT3 ANGPTL4 eNOS3 VEGFA Transcriptional factors Response element 

Supplementary material

12185_2012_1117_MOESM1_ESM.doc (240 kb)
Supplementary material 1 (DOC 239 kb)

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Copyright information

© The Japanese Society of Hematology 2012

Authors and Affiliations

  • Norman E. Buroker
    • 1
  • Xue-Han Ning
    • 2
  • Zhao-Nian Zhou
    • 3
  • Kui Li
    • 4
  • Wei-Jun Cen
    • 4
  • Xiu-Feng Wu
    • 3
  • Wei-Zhong Zhu
    • 3
  • C. Ronald Scott
    • 1
  • Shi-Han Chen
    • 1
  1. 1.Department of PediatricsUniversity of WashingtonSeattleUSA
  2. 2.Division of CardiologySeattle Children’s Hospital, Institute, FoundationSeattleUSA
  3. 3.Laboratory of Hypoxia Physiology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  4. 4.Lhasa People HospitalLhasaChina

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