Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas.
Droma Y., Hanaoka M., Basnyat B., Arjyal A., Neupane P., Pandit A., Sharma D., Miwa N., Ito M., Katsuyama Y., Ota M., Kubo K.
The Sherpas' adaptation to high altitude has been hypothesized as being due to a genetic basis since the beginning of the last century, but this has yet to be demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111 non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in serum were measured. The frequencies of the Glu and eNOS4b alleles were significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas' adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary individually, thus it is not a reliable indicator for endogenous nitric oxide production.