Whole genome association study in high-altitude pulmonary edema

高原肺水肿的全基因组关联研究

• 批准号: 22590853
• 负责人: HANAOKA Masayuki
• 金额: $ 2.41万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590853/
• 关键词: 高地肺水腫; 遺伝子; マイクロサテライトマーカー; TIMP3; 単塩基多型; ゲノム; マイクロサテライト; CLCNKB遺伝子; ゲノムワイド; PCR法

The aim of this study is attempt to identify the candidate human genes those might associate with the development of high-altitude pulmonary edema (HAPE). A case-control association study was performed using 400 polymorphic microsatellite markers by PCR and sequenced byGene Scan software in HAPE susceptible subjects and HAPE resistant subjects. Nine markers showed statistically significant associations with the susceptibility to HAPE, and three markers showed significant associations with the resistance to HAPE. We also evaluated the association of HAPE with six single nucleotide polymorphisms (SNPs) in tissue inhibitor of metalloproteinase 3 (TIMP3) gene, and found that one SNP (rs130293) was significantly associated with the HAPE susceptibility (P < 0.0005). This study provides the first evidence that the development of HAPE may be determined by the interaction of multiply genes and TIMP3 may influence the risk for HAPE.

本研究的目的是寻找可能与高原肺水肿（HAPE）发生相关的人类候选基因。采用PCR扩增400个多态性微卫星标记，并利用基因扫描软件对HAPE易感者和耐药者进行病例对照关联研究。9个标记物与HAPE的易感性有统计学意义，3个标记物与HAPE的耐药性有统计学意义。我们还对组织金属蛋白酶抑制剂3（TIMP3）基因的6个单核苷酸多态性（SNP）与HAPE的相关性进行了研究，发现1个SNP（rs130293）与HAPE的易感性显著相关（P < 0.0005）。本研究首次证明HAPE的发生可能是由多个基因相互作用决定的，TIMP 3可能影响HAPE的发病风险。

项目成果

A Genome wide DNA Microsatellite Association Study of Japanese Patients with High alttitude pulmonary edema (HAPE).

日本高原肺水肿 (HAPE) 患者的全基因组 DNA 微卫星关联研究。

• 发表时间: 2011
• 作者: Nobumitsu Kobayashi;Masao Ota;Masayuki Hanaoka;Yunden Droma;Yoshihiko Katsuyama;Keishi Kubo.
• 通讯作者: Keishi Kubo.

Pulmonary Hypertension Associated with Respiratory Diseases

与呼吸系统疾病相关的肺动脉高压

• 发表时间: 2010
• 作者: Okimoto T;Tsubata Y;Sutani A;Fuchita H;Koba N;Nishikawa E;Hotta T;Okimoto T;Iwamoto S;Karino F;Miura K;Tada M;Suzuki T;Honda T;Hamaguchi S;Ohe M;Sutani A;Kuraki T;Isobe T;花岡正幸
• 通讯作者: 花岡正幸

高地肺水腫の分子遺伝学的検討

高原肺水肿的分子遗传学研究

• 发表时间: 2012
• 作者: 堀内俊道;花岡正幸;太田正穂;小林信光;雲登卓瑪;伊東理子;勝山喜彦;小林俊夫;久保惠嗣
• 通讯作者: 久保惠嗣

Adaptation to high altitude in Sherpas: Genetic contributions of the polymorphisms in the angiotensin-converting enzyme gene and the endothelial nitric oxide synthase gene

夏尔巴人对高海拔的适应：血管紧张素转换酶基因和内皮一氧化氮合酶基因多态性的遗传贡献

• 发表时间: 2010
• 作者: Okimoto T;Tsubata Y;Sutani A;Fuchita H;Koba N;Nishikawa E;Hotta T;Okimoto T;Iwamoto S;Karino F;Miura K;Tada M;Suzuki T;Honda T;Hamaguchi S;Ohe M;Sutani A;Kuraki T;Isobe T;花岡正幸;花岡正幸
• 通讯作者: 花岡正幸