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Clinical Investigations: PULMONARY VASCULAR DISEASE |

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

Junichi Hotta, MD; Masayuki Hanaoka, MD; Yunden Droma, MD; Yoshihiko Katsuyama, PhD; Masao Ota, PhD; Toshio Kobayashi, MD
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*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@hsp.md.shinshu-u.ac.jp



Chest. 2004;126(3):825-830. doi:10.1378/chest.126.3.825
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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.


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