Positive association of the endothelial nitric oxide synthase gene polymorphisms with high-altitude pulmonary edema

被引:117
作者
Droma, Y
Hanaoka, M
Ota, M
Katsuyama, Y
Koizumi, T
Fujimoto, K
Kobayashi, T
Kubo, K
机构
[1] Shinshu Univ, Sch Med, Dept Med, Matsumoto, Nagano 390, Japan
[2] Shinshu Univ, Sch Med, Dept Legal Med, Matsumoto, Nagano 390, Japan
[3] Shinshu Univ, Sch Med, Dept Pharm, Matsumoto, Nagano 390, Japan
关键词
hypoxia; hypertension; pulmonary; genes; nitric oxide synthase;
D O I
10.1161/01.CIR.0000024409.30143.70
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-A defect of nitric oxide (NO) synthesis in the lung of high-altitude pulmonary edema (HAPE) has been suggested to contribute to its exaggerated pulmonary hypertension. Several polymorphisms have been identified in the,gene encoding endothelial nitric oxide synthase (eNOS), which is a key enzyme responsible for NO synthesis, some of which were reported to be associated with vascular disorders. Methods and Results-We studied 41 HAPE-susceptible subjects (HAPE-s) and 51 healthy climbers (control group) in a Japanese population. We examined 2 polymorphisms of the eNOS gene, including the Glu298Asp variant and 27-base pair (bp) variable numbers of tandem repeats using polymerase chain reaction followed by restriction fragment length polymorphism. The Asp allelic frequency of the Glu298Asp variant was 25.6% in the HAPE-s and 9.8% in the controls, which was significantly different between the two groups (P=0.0044). The eNOS4a allelic frequency of 27-bp variable numbers of tandem repeats was 23.2% in the HAPE-s, significantly higher than that of 6.9% in the controls (P=0.0016). In HAPE-s group, 11 of 41 (26.8%) subjects possessed simultaneously both of the two significant alleles, but among the controls, none did, which showed a high statistical difference between the two groups (P=0.000059). Conclusions-Both polymorphisms of the eNOS gene were significantly associated with HAPE. A genetic background may underlie the impaired NO synthesis in the pulmonary circulation of HAPE-s. These polymorphisms could be genetic markers for predicting the susceptibility to HAPE.
引用
收藏
页码:826 / 830
页数:5
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