PMID- 15364762
OWN - NLM
STAT- MEDLINE
DCOM- 20041102
LR  - 20221207
IS  - 0012-3692 (Print)
IS  - 0012-3692 (Linking)
VI  - 126
IP  - 3
DP  - 2004 Sep
TI  - Polymorphisms of renin-angiotensin system genes with high-altitude pulmonary 
      edema in Japanese subjects.
PG  - 825-30
AB  - STUDY OBJECTIVES: 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. DESIGN: 
      A cross-sectional, case-control study. SETTING: Shinshu University Hospital, 
      Matsumoto, Japan. PARTICIPANTS: Forty-nine HAPE-susceptible (HAPE-s) subjects 
      with a history of HAPE, and 55 healthy climbers with HAPE resistance (HAPE-r). 
      INTERVENTIONS: Twenty-one of 49 HAPE-s subjects underwent right cardiac 
      catheterization. MEASUREMENTS AND 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.
FAU - Hotta, Junichi
AU  - Hotta J
AD  - Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 
      Asahi, Matsumoto 390-8621, Japan.
FAU - Hanaoka, Masayuki
AU  - Hanaoka M
FAU - Droma, Yunden
AU  - Droma Y
FAU - Katsuyama, Yoshihiko
AU  - Katsuyama Y
FAU - Ota, Masao
AU  - Ota M
FAU - Kobayashi, Toshio
AU  - Kobayashi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Chest
JT  - Chest
JID - 0231335
RN  - 0 (DNA Transposable Elements)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Altitude Sickness/*genetics
MH  - Asian People/*genetics
MH  - Case-Control Studies
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 13
MH  - Chromosomes, Human, Pair 3
MH  - Cross-Sectional Studies
MH  - DNA Mutational Analysis
MH  - DNA Transposable Elements/genetics
MH  - Female
MH  - Gene Frequency/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genetics, Population
MH  - Hemodynamics/genetics
MH  - Humans
MH  - Japan
MH  - Lung/blood supply
MH  - Male
MH  - Mountaineering
MH  - Peptidyl-Dipeptidase A/genetics
MH  - Phenotype
MH  - Polymorphism, Genetic/*genetics
MH  - Pulmonary Edema/*genetics
MH  - Receptor, Angiotensin, Type 1/genetics
MH  - Renin-Angiotensin System/*genetics
EDAT- 2004/09/15 05:00
MHDA- 2004/11/04 09:00
CRDT- 2004/09/15 05:00
PHST- 2004/09/15 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/09/15 05:00 [entrez]
AID - S0012-3692(15)31225-3 [pii]
AID - 10.1378/chest.126.3.825 [doi]
PST - ppublish
SO  - Chest. 2004 Sep;126(3):825-30. doi: 10.1378/chest.126.3.825.