title: Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas.
abstract: 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.
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yunden
authors.initials: Y
authors.lastname: Droma
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.forename: Amit
authors.initials: A
authors.lastname: Arjyal
authors.forename: Pritam
authors.initials: P
authors.lastname: Neupane
authors.forename: Anil
authors.initials: A
authors.lastname: Pandit
authors.forename: Dependra
authors.initials: D
authors.lastname: Sharma
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miwa
authors.forename: Michiko
authors.initials: M
authors.lastname: Ito
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000235:genetics; D044466:Asian People; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009390:Nepal; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III