Two hypoxia sensor genes and their association with symptoms of acute mountain sickness in Sherpas.
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.
Droma
Yunden
Y
Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
Ota
Masao
M
Hanaoka
Masayuki
M
Katsuyama
Yoshihiko
Y
Basnyat
Buddha
B
Neupane
Pritam
P
Arjyal
Amit
A
Pandit
Anil
A
Sharma
Dependra
D
Ito
Michiko
M
Kubo
Keishi
K
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*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein