title: Polymorphisms of renin-angiotensin system genes with high-altitude pulmonary edema in Japanese subjects.
abstract: OBJECTIVE
  The renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT(1)R), plays an important role in the pathogenesis of pulmonary hypertension, which is suggested to be critical in the development of high-altitude pulmonary edema (HAPE). Investigating the associations of the polymorphisms in the genes of RAS with HAPE is to elucidate the genetic background underlying this disease.
  
  
  METHODS
  A cross-sectional, case-control study.
  
  
  METHODS
  Shinshu University Hospital, Matsumoto, Japan.
  
  
  METHODS
  Forty-nine HAPE-susceptible (HAPE-s) subjects with a history of HAPE, and 55 healthy climbers with HAPE resistance (HAPE-r).
  
  
  METHODS
  Twenty-one of 49 HAPE-s subjects underwent right cardiac catheterization.
  
  
  RESULTS
  The insertion/deletion polymorphism in the ACE gene (ACE-I/D) was investigated by polymerase chain reaction (PCR). There was no significant difference of the distribution of the ACE-I/D polymorphism between the HAPE-s and HAPE-r groups. The A(1166)C and G(1517)T single-nucleotide polymorphisms (SNPs) in AT(1)R gene were investigated by the PCR following digested by corresponding restricted endonuclease enzymes. The distribution of the G(1517)T SNP was significantly different between the two groups (p = 0.012). The pulmonary hemodynamics of the 21 HAPE-s subjects were retrospectively examined. The pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR), and PVR index (PVRI) were all significantly increased on hospital admission. Moreover, the PVR and PVRI were significantly higher in the HAPE-s subjects with D positivity than in the HAPE-s subjects with I positivity (PVR, p = 0.015; PVRI, p = 0.028), while the PAP did not show any significant difference between the two subgroups.
  
  
  CONCLUSIONS
  The ACE-I/D polymorphism is not associated with HAPE susceptibility in Japanese subjects. The AT(1)R gene polymorphisms may likely associate with HAPE susceptibility. The D allele of the ACE-I/D polymorphism probably contributes to the hyperresponsive PVR and PVRI to acute hypoxia.
authors.affiliation: Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hotta
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hanaoka
authors.forename: Yunden
authors.initials: Y
authors.lastname: Droma
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.forename: Toshio
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000328:Adult; D000483:Alleles; D000532:Altitude Sickness / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D002893:Chromosomes, Human, Pair 3; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005828:Genetics, Population; D006439:Hemodynamics / Q000235:genetics; D006801:Humans; D007564:Japan; D008168:Lung / Q000098:blood supply; D008297:Male; D009051:Mountaineering; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011654:Pulmonary Edema / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D044140:Receptor, Angiotensin, Type 1; D007703:Peptidyl-Dipeptidase A