Hotta Junichi, Hanaoka Masayuki, Droma Yunden, Katsuyama Yoshihiko, Ota Masao, Kobayashi Toshio
Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
Chest. 2004 Sep;126(3):825-30. doi: 10.1378/chest.126.3.825.
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.
A cross-sectional, case-control study.
Shinshu University Hospital, Matsumoto, Japan.
Forty-nine HAPE-susceptible (HAPE-s) subjects with a history of HAPE, and 55 healthy climbers with HAPE resistance (HAPE-r).
Twenty-one of 49 HAPE-s subjects underwent right cardiac catheterization.
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.
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.
肾素 - 血管紧张素系统（RAS），包括血管紧张素转换酶（ACE）和血管紧张素II 1型受体（AT(1)R），在肺动脉高压的发病机制中起重要作用，而肺动脉高压被认为在高原肺水肿（HAPE）的发展中至关重要。研究RAS基因多态性与HAPE的关联旨在阐明该疾病的遗传背景。
一项横断面病例对照研究。
日本松本市信州大学医院。
49名有HAPE病史的HAPE易感（HAPE - s）受试者，以及55名具有HAPE抵抗力的健康登山者（HAPE - r）。
49名HAPE - s受试者中的21名接受了右心导管检查。
通过聚合酶链反应（PCR）研究ACE基因中的插入/缺失多态性（ACE - I/D）。HAPE - s组和HAPE - r组之间ACE - I/D多态性的分布没有显著差异。通过相应限制性内切酶消化后的PCR研究AT(1)R基因中的A(1166)C和G(1517)T单核苷酸多态性（SNP）。两组之间G(1517)T SNP的分布有显著差异（p = 0.012）。对21名HAPE - s受试者的肺血流动力学进行了回顾性检查。入院时肺动脉压（PAP）、肺血管阻力（PVR）和PVR指数（PVRI）均显著升高。此外，D阳性的HAPE - s受试者的PVR和PVRI显著高于I阳性的HAPE - s受试者（PVR，p = 0.015；PVRI，p = 0.028），而两个亚组之间的PAP没有显示出任何显著差异。
ACE - I/D多态性与日本受试者的HAPE易感性无关。AT(1)R基因多态性可能与HAPE易感性相关。ACE - I/D多态性的D等位基因可能导致PVR和PVRI对急性缺氧的高反应性。
