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.
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.
Authors: Zudin Puthucheary; James R A Skipworth; Jai Rawal; Mike Loosemore; Ken Van Someren; Hugh E Montgomery Journal: Sports Med Date: 2011-06-01 Impact factor: 11.136
Authors: Kevin R Barker; Andrea L Conroy; Michael Hawkes; Holly Murphy; Prativa Pandey; Kevin C Kain Journal: J Travel Med Date: 2016-03-16 Impact factor: 8.490
Authors: Abigail Bigham; Marc Bauchet; Dalila Pinto; Xianyun Mao; Joshua M Akey; Rui Mei; Stephen W Scherer; Colleen G Julian; Megan J Wilson; David López Herráez; Tom Brutsaert; Esteban J Parra; Lorna G Moore; Mark D Shriver Journal: PLoS Genet Date: 2010-09-09 Impact factor: 5.917