Affiliation:
1. From the Departments of Medicine (Y.D., M.H., T. Koizumi, K.F., T. Kobayashi, K.K.), Legal Medicine (M.O.), and Pharmacy (Y.K.), Shinshu University School of Medicine, Matsumoto, Japan.
Abstract
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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Cited by
114 articles.
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