title: Lack of evidence for association of high altitude pulmonary edema and polymorphisms of the NO pathway.
abstract: One essential factor in the development of high altitude pulmonary edema (HAPE) is elevated pulmonary artery pressure, possibly due to a lack of nitric oxide (NO) in pulmonary vessels. NOS3 gene polymorphisms (G894T, T-786C, and CA-repeats > or =38) might be linked to decreased NO synthesis and increased susceptibility to HAPE, while the C242T polymorphism of the CYBA gene [encoding for the NAD(P)H oxidase subunit p22phox] may increase NO availability and thus convey resistance to HAPE. To test this hypothesis, we genotyped 51 mountaineers susceptible and 52 mountaineers not susceptible to HAPE. Genotyping revealed similar genotype frequencies of the G894T and the T-786C NOS3 polymorphism in both groups (G894T: susceptibles, 39.2% GG, 47.1% GT, 13.7% TT; nonsusceptibles, 48.0% GG, 44.0% GT, 8.0% TT; p = 0.54. T-786C: susceptibles, 45.1% TT, 39.2% TC, 15.7% CC; nonsusceptibles, 53.8% TT, 40.4% TC, 5.8% CC; p = 0.28). Genotype frequencies of the C242T CYBA polymorphism were 43.1% CC, 47.1 % CT, and 9.8% TT in HAPE susceptibles and 38.0% CC, 52.0 % CT, and 10.0% TT (p = 0.92) in nonsusceptibles. There was also no difference between the two groups in the number of CA repeats (p = 0.57), and individuals with > or =38 CA repeats were not more likely to develop HAPE (p = 1.0). Haplotype analysis for the NOS3 polymorphisms also revealed no association with HAPE. The results of this study suggest that none of these genetic variants plays a substantial role in the pathogenesis of HAPE in Caucasians, but does not exclude epistatic effects that might still involve the genetic systems studied here.
authors.affiliation: Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Bergheimer Strasse 58, D-69115 Heidelberg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Weiss
authors.forename: Walter Emil
authors.initials: WE
authors.lastname: Haefeli
authors.forename: Christiane
authors.initials: C
authors.lastname: Gasse
authors.forename: Michael Marcus
authors.initials: MM
authors.lastname: Hoffmann
authors.forename: Jörn
authors.initials: J
authors.lastname: Weyman
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbs
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mansmann
authors.forename: Peter
authors.initials: P
authors.lastname: Bärtsch
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D009051:Mountaineering; D009252:NADPH Dehydrogenase / Q000235:genetics; D019255:NADPH Oxidases; D009569:Nitric Oxide / Q000235:genetics* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D016017:Odds Ratio; D010750:Phosphoproteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011654:Pulmonary Edema / Q000209:etiology / Q000235:genetics* / Q000378:metabolism
chemical_list: D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase