title: Two hypoxia sensor genes and their association with symptoms of acute mountain sickness in Sherpas.
abstract: BACKGROUND
  Hypoxia-inducible factor (HIF) and von Hippel-Lindau tumor suppressor protein (VHL) are hypoxia sensors that control cellular responses to hypoxia. Although many Sherpas live at high altitudes for their entire lives, some of them manifest symptoms of acute mountain sickness (AMS) during mountaineering at extremely high altitudes. We hypothesize that the two hypoxia sensor genes might associate with the occurrence of AMS symptoms in Sherpas at extremely high altitude.
  
  
  METHODS
  In a village at an altitude of 3440 m, 104 Sherpas who had mountaineered at extremely high altitudes (over 5000 m) were divided into two groups: Sherpas with (N = 45) and without (N = 59) histories of AMS symptoms. The rs11549465 SNP in the HIF-1alpha gene (HIF1A) and the rs28940298, rs779805, rs779808, rs1678607, and 1149A > G SNPs in the VHL gene (VHL) were identified in the two Sherpa groups using PCR following RFLP.
  
  
  RESULTS
  There were no significant differences in ei-ther the genotype distributions or the allele frequencies of the HIF1A and VHL genetic variants between the two Sherpa groups.
  
  
  CONCLUSIONS
  These genetic variants of HIF1A and VHL are not associated with AMS symptoms that occur in Sherpas at extremely high altitudes. It seems unlikely that HIF1A and VHL are associated with hypoxic sensing sensitivity in Sherpas.
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yunden
authors.initials: Y
authors.lastname: Droma
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Pritam
authors.initials: P
authors.lastname: Neupane
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.forename: Anil
authors.initials: A
authors.lastname: Pandit
authors.forename: Dependra
authors.initials: D
authors.lastname: Sharma
authors.forename: Michiko
authors.initials: M
authors.lastname: Ito
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000532:Altitude Sickness / Q000235:genetics*; D044466:Asian People; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D009390:Nepal; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044382:Population Groups / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein