title: Positive association of the endothelial nitric oxide synthase gene polymorphisms with high-altitude pulmonary edema.
abstract: BACKGROUND
  A defect of nitric oxide (NO) synthesis in the lung of high-altitude pulmonary edema (HAPE) has been suggested to contribute to its exaggerated pulmonary hypertension. Several polymorphisms have been identified in the gene encoding endothelial nitric oxide synthase (eNOS), which is a key enzyme responsible for NO synthesis, some of which were reported to be associated with vascular disorders.
  
  
  RESULTS
  We studied 41 HAPE-susceptible subjects (HAPE-s) and 51 healthy climbers (control group) in a Japanese population. We examined 2 polymorphisms of the eNOS gene, including the Glu298Asp variant and 27-base pair (bp) variable numbers of tandem repeats using polymerase chain reaction followed by restriction fragment length polymorphism. The Asp allelic frequency of the Glu298Asp variant was 25.6% in the HAPE-s and 9.8% in the controls, which was significantly different between the two groups (P=0.0044). The eNOS4a allelic frequency of 27-bp variable numbers of tandem repeats was 23.2% in the HAPE-s, significantly higher than that of 6.9% in the controls (P=0.0016). In HAPE-s group, 11 of 41 (26.8%) subjects possessed simultaneously both of the two significant alleles, but among the controls, none did, which showed a high statistical difference between the two groups (P=0.000059).
  
  
  CONCLUSIONS
  Both polymorphisms of the eNOS gene were significantly associated with HAPE. A genetic background may underlie the impaired NO synthesis in the pulmonary circulation of HAPE-s. These polymorphisms could be genetic markers for predicting the susceptibility to HAPE.
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: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Koizumi
authors.forename: Keisaku
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Keishi
authors.initials: K
authors.lastname: Kubo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000531:Altitude; D019943:Amino Acid Substitution / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006439:Hemodynamics / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000172:deficiency / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011652:Pulmonary Circulation / Q000235:genetics; D011654:Pulmonary Edema / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III