A novel function of membrane cholesterol transporter and a therapeutic strategy for atherosclerosis

• Project/Area Number: 19590874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Fukuoka University
• Principal Investigator: UEHARA Yoshinari Fukuoka University, 医学部, 講師 (70373149)
• Co-Investigator(Kenkyū-buntansha): SAKU Keijiro 福岡大学, 医学部, 教授 (40183371) ; MATSUNAGA Yoichi 徳島文理大学, 薬学部, 教授 (80239053) ; YAMADA Tatsuo 福岡大学, 医学部, 教授 (60159217)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂質 / 循環器・高血圧 / 高比重リポ蛋白 / 発現制御 / 遺伝子多型 / リポ蛋白 / アポリポ蛋白 / 臨床 / 遺伝子

Research Abstract

A novel -257T>G single nucleotide polymorphism (SNP) was found in ATP-Binding Cassette Transporter (ABC) G1 promoter. The -257T>G SNP had a reduced transcriptional activity of ABCG1 invitro. In the clinical analysis of ABCG1 -257T>G SNP, although ABCG1 was not related with plasma cholesterol levels, it was shown that ABCG1 had affected to a lipoprotein composition such as HDL prticle in patients with ischemic heart disease. This is a new finding to show that ABCG1 contributes to protect a progression of atherosclerosis.

Research Products

• [Journal Article] Homocysteine Induced Oxidative Stress Upregulates Chymase in Mouse Mastocytoma Cells (2010)
  • Author(s): Kanta Fujimi, Yoshinari Uehara, Satomi Abe, Akira Kawamura, Sankar Devarajan, Shin-ichiro Miura, Keijiro Saku, Hidenori Urata
  • Journal Title: Hypertens Res 33(2) Pages: 149-154
  • NAID: 10026126394
  • Peer Reviewed
• [Journal Article] Homocysteine-induced oxidative stress upregulates chymase in mouse mastocytoma cells (2010)
  • Author(s): Fujimi, K., Uehara, Y., Abe, S., Kawamura, A., Devarajan, S., Miura, S., Saku, K., Urata, H.
  • Journal Title: Hypertens Res 33 Pages: 149-154
  • NAID: 10026126394
  • Peer Reviewed
• [Journal Article] Genotypic effect of ABCG1 gene promoter-257T>G polymorphism on coronary artery disease severity in Japanese men (2009)
  • Author(s): Furuyama S, Uehara Y, Zhang B, Baba Y, Abe S, Iwamoto T, Miura SI, Saku K.
  • Journal Title: J Atheroscler Thromb 16 Pages: 194-200
  • NAID: 10025765477
  • Peer Reviewed
• [Journal Article] Newly developed PPAR-alpha agonist (R)-K-13675 inhibits the secretion of inflammatory markers without affecting cell proliferation or tube formation. (2009)
  • Author(s): Kitajima K, Miura SI, Mastuo Y, Uehara Y, Saku K.
  • Journal Title: Atherosclerosis 203(1) Pages: 75-81
  • Peer Reviewed
• [Journal Article] A postmenopausal patient with Tangier disease developing Sjogren's syndrome. (2009)
  • Author(s): Miyachi K, Hankins RW, Uehara Y, Zhang B, Saku K, Homma Y, Shigematsu H, Mikoshiba K.
  • Journal Title: J Rheumatol 36(1) Pages: 208-10
  • Peer Reviewed
• [Journal Article] 特集:HDLを再考する-わが国のHDL関連遺伝子異常とCardiovascular Riskを知る (2009)
  • Author(s): 上原吉就, 朔啓二郎
  • Journal Title: Vascular Medicine 5(2) Pages: 100-105
• [Journal Article] Genotypic Effect of ABCG1 gene promoter -257T>G polymorphism on coronary artery disease severity in Japanese men (2009)
  • Author(s): Furuyama, S., Uehara, Y., Zhang, B., Baba, Y., Abe, S., Iwamoto, T., Miura, S., Saku, K.
  • Journal Title: J Atheroscler Thromb 16 Pages: 194-200
  • NAID: 10025765477
  • Peer Reviewed
• [Journal Article] Genotypic effect of ABCG1 gene promoter -257T>G polymorphism on coronary artery disease severity in Japanese men (2009)
  • Author(s): Furuyama. S, Uehara. Y, et al.
  • Journal Title: Journal of Atherosclerosis and Thrombosis (in press)
  • NAID: 10025765477
  • Peer Reviewed
• [Journal Article] ATP-binding cassette transporter G4 is highly expressed in microglia in Alzheimer's brain. (2008)
  • Author(s): Uehara Y, Yamada T, Baba Y, Miura SI, Abe S, Kitajima K, Higuchi MA, Iwamoto T, Saku K.
  • Journal Title: Brain Res 1217C Pages: 239-246
  • Peer Reviewed
• [Journal Article] ATP-binding cassette transporter G4 is highly expressed in microglia in Alzheimer's brain. (2008)
  • Author(s): Uehara. Y, et al.
  • Journal Title: Brain Research 1217C Pages: 239-246
  • Peer Reviewed
• [Presentation] Identification and Cloning of Novel Soluble and Membrane Bound Forms of The Human ATP-Binding Cassette Transporter G4. (2010)
  • Author(s): Y. Uehara, S. Abe, E. Yahiro, A. Kawamura, T. Iwamoto, SI. Miura, K. Saku
  • Organizer: The 72st Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 京都
  • Year and Date: 2010-03-07
• [Presentation] シンポジウム)Low HDL-C: Role of lipid transporters and apoA-I mimetic peptides (2008)
  • Author(s): 上原吉就
  • Organizer: 第40回日本動脈硬化学会総会
  • Place of Presentation: つく1ま
  • Year and Date: 2008-07-11
• [Presentation] A Severity of Coronary Artery Disease is influenced by ATP-binding Cassette Transporter G1(ABCG1) -257T>G Promoter Polymorphism. (2008)
  • Author(s): Uehara Y, Funlyama S, Abe S, Okamura K, Miura S, Iwamoto T, Saku K.
  • Organizer: The 77th European Atherosclerosis Society Congress
  • Place of Presentation: Istanbul
  • Year and Date: 2008-04-27
• [Presentation] A Severity of Coronary Artery Disease is influenced by ATP-binding Cassette Transporter G1 (ABCG1) -257T>G Promoter Polymorphism. (2008)
  • Author(s): 上原吉就, ら
  • Organizer: 第77回欧州動脈硬化学会
  • Place of Presentation: イスタンブール(トルコ)
  • Year and Date: 2008-04-27
• [Presentation] ATP-binding cassette transporter G4 (ABCG4) is highly expressed in Alzheimer brain (2007)
  • Author(s): Y. Uehara, M. Higuchi, Y. Baba, T. Iwamoto, T. Yamada
  • Organizer: The 25th International Psychogeriatric Association Congress
  • Place of Presentation: Osaka
  • Year and Date: 2007-10-17
• [Presentation] ATP-binding Cassette Transporter G1(ABCG1)遺伝子プロモーター多型は冠動脈病変重症度と関連する (2007)
  • Author(s): 古山正大, 上原吉就, 阿部智美, 岡村圭祐, 三浦伸一郎, 張波, 朔啓二郎
  • Organizer: 第39回日本動脈硬化学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-14
• [Presentation] ATP-binding Cassette Transporter G1 (ABCGI)遺伝子プロモーター多型(T-257G)はスタチンの作用を減弱する (2007)
  • Author(s): 岡村圭祐, 上原吉就, 張波, 三浦伸一郎, 古山正大, 阿部智美, 浦田秀則, 朔啓二郎
  • Organizer: 第39回日本動脈硬化学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-14
• [Presentation] ATP-binding Cassette Transporter Gl(ABCGI)遺伝子プロモーター多型(T-257G)は冠動脈重症度と関連する (2007)
  • Author(s): 古山 正大
  • Organizer: 第39回日本動脈硬化学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-13
• [Book] 新・心臓病診療プラクティス心血管イベントのリスクファクターとその管理 (2009)
  • Author(s): 上原吉就, 朔啓二郎
  • Publisher: 文光堂
• [Remarks]
  • URL: http://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/4089/R110J.html?P=SunJun621:05:42UTC+09002010
• [Remarks]
  • URL: http://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/4089/R110J.html?P=FriMay1415:02:04UTC+09002010
• [Remarks]
  • URL: http://resweb2.jhk.adm.fukuoka-u.ac.jp/FukuokaUnivHtml/info/4089/R110J.html?P=Tue%20May%2019%2016:56:24%20UTC+0900%202009