Polymorphisms of hypoxia-related genes in subjects susceptible to acute mountain sickness

Background: The occurrence of acute mountain sickness (AMS), which develops in some individuals who ascend to altitudes above 2,500 m, may be associated with 4 hypoxia-related genes (HIF-1, VEGFA, HSP-70 and eNOS).

Objectives: The aim of our study was to investigate the potential role of the 4 hypoxia-related genes in AMS pathogenesis. We therefore evaluated single-nucleotide polymorphisms (SNPs) of the genes in an association study using a case-control design.

Methods: At an altitude of 4,600 m, 64 male Chinese patients with AMS, defined according to the Lake Louise consensus criteria, were compared to 64 Chinese men free of symptoms of AMS. Clinical data, such as age, history of diseases, oxygen saturation (SpO(2)) and heart rate, were obtained. Genotypes of selected SNPs of these genes in patients were compared with those in controls.

Results: The mean SpO(2) and heart rate of the AMS and control groups were similar before ascent to high altitude (p = 0.79, p = 0.62) but, 24 h after ascent, the mean SpO(2) of the AMS group was significantly lower than that of the control group (p = 0.001), and the mean heart rate of the AMS group was significantly higher than that of the control group (p = 0.001). Twenty-eight of the 48 SNPs investigated were successfully genotyped, and SNP allele frequencies were obtained. The rs3025039 SNP and the haplotype (rs1413711, rs833070 and rs3025000) in the VEGFA gene were significantly associated with AMS (p = 0.0435 and 0.024, respectively).

Conclusions: Our study demonstrates a possible association between the VEGFA gene and AMS. We conclude that VEGFA may have an important role in the AMS process.