A genome wide DNA microsatellite association study of Japanese patients with high altitude pulmonary edema

医学 高原肺水肿 候选基因 内科学 基因 遗传学 肺水肿 生物
作者
Nobumitsu Kobayashi,Masao Ôta,Masayuki Hanaoka,Yunden Droma,Michiko Ito,Yoshihiko Katsuyama,Hideki Asamura,Keishi Kubo
出处
期刊:European Respiratory Journal 卷期号:38: 4914-
摘要

Introduction: High altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that develops in susceptible people who ascend quickly to high altitude. The pathogenesis remains to be conclusively elucidated and genetic polymorphisms were highly proposed to be associated with HAPE. The aim of this study is attempt to identify the locations of the candidate human genes those might associate with the HAPE susceptibility or resistance. Methods: The case group included 53 Japanese HAPE susceptible subjects (HAPE-s) who had developed HAPE during climbing mountains higher than 2500m and the control group enrolled 67 HAPE Japanese resistant subjects (HAPE-r) who were Japanese Alpinist and did not develop HAPE during their histories. A case-control association study was performed using 400 polymorphic microsatellite markers (which define about 10 centiMorgan resolution throughout the whole genome) by PCR. The PCR-amplified products were sequenced automatically by Gene Scan software. Results: Nine markers (D1S468, D1S2697, D1S2785, D4S405, D5S424, D6S257, D12S2638, D16S3103 and D21S263) showed statistically significant associations with the susceptibility to HAPE, and three markers (D1S230, D14S283 and D22S280) showed significant associations with the resistance to HAPE. These markers were in linkage with genes controlling pulmonary alveolus structure, chloride channel, endocrine proteins, and other factors those might play important roles in the development of HAPE. Conclusion: This is the first genomewide association study in HAPE. It revealed several candidate genes in associations with HAPE. The development of HAPE may be determined by the interaction of multiply genes.

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