Whole genome association study in high-altitude pulmonary edema

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590853
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Shinshu University
• Principal Investigator: HANAOKA Masayuki 信州大学, 医学部, 准教授 (20334899)
• Co-Investigator(Kenkyū-buntansha): OTA Masao 信州大学, 医学部, 准教授 (50115333) ; ITO Michiko 信州大学, 医学部附属病院, 医員 (60569812)
• Project Period (FY): 2010 – 2012
• Keywords: 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

Research Abstract

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.

Research Products

• [Presentation] A Genome Wide DNA Microsatellite Association Study and Association of TIMP3 gene Polymorphism in Japanese Patients with High Altitude Pulmonary Edema (HAPE). (2013)
  • Author(s): Nobumitsu Kobayashi, Masayuki Hanaoka, Masao Ota, Fumiya Kinota, Yunden Droma, Michiko Ito, Masanori Yasuo , Yo shi hi ko Kat suyama, Hi de ki Asamura, Keishi Kubo.
  • Organizer: 5th World Symposium of Pulmonary Hypertension
  • Place of Presentation: Nice, France
  • Year and Date: 2013-02-27
• [Presentation] 高地肺水腫の分子遺伝学的検討 (2012)
  • Author(s): 小林信光、花岡正幸、太田正穂、雲登卓瑪、伊東理子、勝山喜彦、小林俊夫、久保惠嗣
  • Organizer: 第32回日本登山医学会学術集会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-06-16
• [Presentation] 高地肺水腫の分子遺伝学的検討 (2012)
  • Author(s): 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
  • Organizer: 第52回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸市
  • Year and Date: 2012-04-22
• [Presentation] A Genome wide DNA Microsatellite Association Study of Japanese Patients with High alttitude pulmonary edema (HAPE). (2011)
  • Author(s): Nobumitsu Kobayashi, Masao Ota, Masayuki Hanaoka, Yunden Droma, Yoshihiko Katsuyama, Keishi Kubo.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Amsterdam, Holland
  • Year and Date: 2011-09-28
• [Presentation] Genome Wide DNA Microsatellite Association Study of Japanese Patients with High Altitude Pulmonary Edema (HAPE). (2011)
  • Author(s): Nobumitsu Kobayashi, Masayuki Hanaoka, Masao Ota, Yunden Droma, Michiko Ito, Yoshihiko Katsuyama, Toshio Kobayashi, Hideki Asamura, Keishi Kubo.
  • Organizer: 2nd Congress of Asia Pacific Society for Mountain Medicine
  • Place of Presentation: Xining, China
  • Year and Date: 2011-08-22
• [Presentation] マイクロサテライト解析法による、日本人の高地肺水腫患者の遺伝学的検討 (2011)
  • Author(s): 小林信光、太田正穂、花岡正幸、雲登卓瑪、伊東理子、勝山喜彦、浅村英樹、久保惠嗣
  • Organizer: 第31回日本登山医学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-11