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2010 Fiscal Year Annual Research Report

血管内皮増殖因子およびその受容体の遺伝子多型を用いた加齢黄斑変性の個別化治療

Research Project

Project/Area Number 22791653
Research InstitutionKyoto University

Principal Investigator

山城 健児  京都大学, 医学研究科, 助教 (80399617)

Keywords加齢黄斑変性 / 血管内皮増殖因子 / 遺伝子多型
Research Abstract

加齢黄斑変性は社会的中途失明の原因として注目されており、その発症には血管内皮増殖因子(VEGF)が関与していることが知られている。しかし、VEGF遺伝子多型と加齢黄斑変性の発症との相関は解明途上であり、本研究では発症との相関および臨床病態との相関を検討した。
まず、日本人の加齢黄斑変性患者および対照群から得られた血液サンプルを使用してVEGF遺伝子中のtag SNP(rs699946、rs699947、rs3025033、rs3025035)と加齢黄斑変性発症との関連を検計した。上記の4つのSNPはすべて広義加齢黄斑変性の発症には相関を認めなかった。さらに広義加齢黄斑変性を狭義加齢黄斑変性とポリープ状脈絡膜血管症のサブタイプに分類して、VEGF遺伝子多型がその発症に相関を持つかどうかも検討したが、いずれのSNPも狭義加齢黄斑変性とポリープ状脈絡膜血管症ともに発症に相関を認めなかった。
次に、広義加齢黄斑変性に対する治療効果との相関を検討した。今回検討した治療方法は抗VEGF治療薬の単独使用および抗VEGF薬にステロイド剤および光線力学療法を併用した2種類の治療である。上記4つのSNPのうち、rs699946で上記2種類の治療を行った後の視力予後と相関を認め、G対立遺伝子を持つ患者では治療後1年間の視力変化が有意に良好であった。しかし、1年回に必要とした治療の回数や、治療後の再発の有無には相関を示さなかった。
今後はVEGF受容体についても検討を加え、さらにそれらの遺伝子多型を利用した個別化医療の実現を目指したいと考えている。

  • Research Products

    (15 results)

All 2011 2010

All Journal Article (15 results) (of which Peer Reviewed: 15 results)

  • [Journal Article] Association of Lesion Size and Visual Prognosis to Polypoidal Choroidal Vasculopathy.2011

    • Author(s)
      Tsujikawa A, Ojima Y, Yamashiro K, Nakata I, Ooto S, Tamura H, Nakanishi H, Hayashi H, Otani A, Yoshimura N.
    • Journal Title

      Am J Ophthalmol.

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Genetic Variants in Pigment Epithelium-Derived Factor Influence Response of Polypoidal Choroidal Vasculopathy to Photodynamic Therapy.2011

    • Author(s)
      Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, Tsujikawa A, Otani A, Ooto S, Tamura H, Saito M, Saito K, Iida T, Oishi A, Kurimoto Y, Matsuda F, Yoshimura N.
    • Journal Title

      Ophthalmology.

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Association of 15q14 and 15q25 with High Myopia in Japanese.2011

    • Author(s)
      Hayashi H, Yamashiro K, Nakanishi H, Nakata I, Kurashige Y, Tsujikawa A, Moriyama M, Ohno-Matsui K, Mochizuki M, Ozaki M, Yamada R, Matsuda F, Yoshimura N.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: (in press)

    • Peer Reviewed
  • [Journal Article] Retinal microstructural abnormalities in central serous chorioretinopathy and polypoidal choroidal vasculopathy.2011

    • Author(s)
      Ooto S, Tsujikawa A, Mori S, Tamura H, Yamashiro K, Otani A, Yoshimura N.
    • Journal Title

      Retina.

      Volume: 31 Pages: 527-534

    • Peer Reviewed
  • [Journal Article] Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical neovascular age-related macular degeneration or polypoidal choroidal vasculopathy.2010

    • Author(s)
      Gotoh N, Yamashiro K, Nakanishi H, Saito M, Iida T, Yoshimura N.
    • Journal Title

      Jpn J Ophthalmol.

      Volume: 54 Pages: 609-614

    • Peer Reviewed
  • [Journal Article] Macular hole formation following photodynamic therapy combined with intravitreal injection of bevacizumab and triamcinolone acetonide.2010

    • Author(s)
      Iwama D, Ooto S, Tsujikawa A, Yamashiro K, Yoshimura N.
    • Journal Title

      Jpn J Ophthalmol.

      Volume: 54 Pages: 364-366

    • Peer Reviewed
  • [Journal Article] Treatment of polypoidal choroidal vasculopathy by intravitreal injection of bevacizumab.2010

    • Author(s)
      Tsujikawa A, Ooto S, Yamashiro K, Tamura H, Otani A, Yoshimura N.
    • Journal Title

      Jpn J Ophthalmol.

      Volume: 54 Pages: 310-319

    • Peer Reviewed
  • [Journal Article] Joint effect of cigarette smoking and CFH and LOC387715/HTRA1 polymorphisms on polypoidal choroidal vasculopathy.2010

    • Author(s)
      Nakanishi H, Yamashiro K, Yamada R, Gotoh N, Hayashi H, Nakata I, Saito M, Iida T, Oishi A, Kurimoto Y, Matsuo K, Tajima K, Matsuda F, Yoshimura N.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 51 Pages: 6183-6187

    • Peer Reviewed
  • [Journal Article] High-resolution imaging of resolved central serous chorioretinopathy using adaptive optics scanning laser ophthalmoscopy.2010

    • Author(s)
      Ooto S, Hangai M, Sakamoto A, Tsujikawa A, Yamashiro K, Ojima Y, Yamada Y, Mukai H, Oshima S, Inoue T, Yoshimura N.
    • Journal Title

      Ophthalmology.

      Volume: 117 Pages: 1800-1809

    • Peer Reviewed
  • [Journal Article] Relationship between retinal sensitivity and morphologic changes in eyes with confluent soft drusen.2010

    • Author(s)
      Iwama D, Tsujikawa A, Ojima Y, Nakanishi H, Yamashiro K, Tamura H, Ooto S, Yoshimura N.
    • Journal Title

      Clin Experiment Ophthalmol.

      Volume: 38 Pages: 483-488

    • Peer Reviewed
  • [Journal Article] CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation.2010

    • Author(s)
      Hayashi H, Yamashiro K, Gotoh N, Nakanishi H, Nakata I, Tsujikawa A, Otani A, Saito M, Iida T, Matsuo K, Tajima K, Yamada R, Yoshimura N.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 51 Pages: 5914-5919

    • Peer Reviewed
  • [Journal Article] Single-nucleotide polymorphisms in the promoter region of matrix metal loproteinase-1, -2, and -3 in Japanese with high myopia.2010

    • Author(s)
      Nakanishi H, Hayashi H, Yamada R, Yamashiro K, Nakata I, Shimada N, Ohno-Matsui K, Mochizuki M, Ozaki M, Yoshitake S, Kuriyama S, Saito M, Iida T, Matsuo K, Matsuda F, Yoshimura N.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 51 Pages: 4432-4436

    • Peer Reviewed
  • [Journal Article] Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.2010

    • Author(s)
      Chen W, Stambolian D, Edwards AO, Branham KE, Othman M, Jakobsdottir J, Tosakulwong N, Pericak-Vance MA, Campochiaro PA, Klein ML, Tan PL, Conley YP, Kanda A, Kopplin L, Li Y, Augustaitis KJ, Karoukis AJ, Scott WK, Agarwal A, Kovach JL, Schwartz SG, Postel EA, Brooks M, Baratz KH, Brown WL ; Complications of Age-Related Macular Degeneration Prevention Trial Research Group, Brucker AJ, Orlin A, Brown G, Ho A, Regillo C, Donoso L, Tian L, Kaderli B, Hadley D, Hagstrom SA, Peachey NS, Klein R, Klein BE, Gotoh N, Yamashiro K, Ferris Iii F, Fagerness JA, Reynolds R, Farrer LA, Kim IK, Miller JW, Corton M, Carracedo A, Sanchez-Salorio M, Pugh EW, Doheny KF, Brion M, Deangelis MM, Weeks DE, Zack DJ, Chew EY, Heckenlively JR, Yoshimura N, Iyengar SK, Francis PJ, Katsanis N, Seddon JM, Haines JL, Gorin MB, Abecasis GR, Swaroop A.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 107 Pages: 7401-7406

    • Peer Reviewed
  • [Journal Article] Thickness of photoreceptor layers in polypoidal choroidal vasculopathy and central serous chorioretinopathy.2010

    • Author(s)
      Ooto S, Tsujikawa A, Mori S, Tamura H, Yamashiro K, Yoshimura N.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 248 Pages: 1077-1086

    • Peer Reviewed
  • [Journal Article] Punctate hyperfluorescent spots associated with central serous chorioretinopathy as seen on indocyanine green angiography.2010

    • Author(s)
      Tsujikawa A, Ojima Y, Yamashiro K, Ooto S, Tamura H, Nakagawa S, Yoshimura N.
    • Journal Title

      Retina

      Volume: 30 Pages: 801-809

    • Peer Reviewed

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Published: 2012-07-19  

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