HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:
Guest Access | Sign In via User Name/Password

This Article Full Text Free Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Hotta, J. Articles by Kobayashi, T. Search for Related Content PubMed PubMed Citation Articles by Hotta, J. Articles by Kobayashi, T.

Polymorphisms of Renin-Angiotensin System Genes With High-Altitude Pulmonary Edema in Japanese Subjects^*

^* From the Departments of Internal Medicine (Drs. Hotta, Hanaoka, Droma, and Kobayashi), Pharmacy (Dr. Katsuyama), and Legal Medicine (Dr. Ota), Shinshu University School of Medicine, Matsumoto, Japan.

Correspondence to: Masayuki Hanaoka, MD, Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan; e-mail: masayuki{at}hsp.md.shinshu-u.ac.jp

Study objectives: The renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT₁R), 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 A¹¹⁶⁶C and G¹⁵¹⁷T single-nucleotide polymorphisms (SNPs) in AT₁R gene were investigated by the PCR following digested by corresponding restricted endonuclease enzymes. The distribution of the G¹⁵¹⁷T 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 AT₁R 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.

Key Words: high-altitude • Japanese • polymorphisms • pulmonary hemodynamics • renin-angiotensin system

This article has been cited by other articles:

				A. Ahsan, G. Mohd, T. Norboo, M. A. Baig, and M. A. Q. Pasha Heterozygotes of NOS3 Polymorphisms Contribute to Reduced Nitrogen Oxides in High-Altitude Pulmonary Edema. Chest, November 1, 2006; 130(5): 1511 - 1519. [Abstract] [Full Text] [PDF]