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医療

2011 Fiscal Year Annual Research Report

• Project/Area Number: 22791653
• Research Institution: Kyoto 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 / 血管内皮前駆細胞 / 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および治療効果との相関を検討したところ、発症には相関を認めなかったが、rs699946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年間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。
一方で、滲出型加齢黄斑変性と同様に脈絡膜新生血管を発症し得る病態に強度近視がある。そこで、VEGF遺伝子の多型が強度近視眼における脈絡膜新生血管の発症および進展に相関を持つかどうかを検討したところ、発症には相関を認めなかったが、新生血管のサイズに相関を認めることが分かった。これらの研究結果から、滲出型加齢黄斑変性、強度近視ともに、脈絡膜新生血管を生じた際にはVEGF遺伝子多型を調べることによって、その予後・治療反応性が予測できると考えられたため、今後はVEGF rs699946の迅速診断キットを作成し、個別化医療を実現していく予定である。

Research Products

• [Journal Article] Factors Associated With the Response of Age-Related Macular Degeneration to Intravitreal Ranibizumab Treatment (2012)
  • Author(s): Yamashiro K, Tomita K, Tsujikawa A, Nakata I, Akagi-Kurashige Y, Miyake M, Ooto S, Tamura H, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Vascular endothelial growth factor gene polymorphisms and choroidal neovascularization in highly myopic eyes (2012)
  • Author(s): Akagi-Kurashige Y, Kumagai K, Yamashiro K, Nakanishi H, Nakata I, Miyake M, Tsujikawa A, Moriyama M, Ohno-Matsui K, Mochizuki M, Yamada R, Matsuda F, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: (in press)
  • DOI: iovs.11-9405[pii]10.1167/iovs.11-9405
  • Peer Reviewed
• [Journal Article] Macular Choroidal Thickness and Volume in Eyes With Angioid Streaks Measured by Swept Source Optical Coherence Tomography (2012)
  • Author(s): Ellabban AA, Tsujikawa A, Matsumoto A, Ogino K, Hangai M, Ooto S, Yamashiro K, Akiba M, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: (in press)
  • DOI: S0002-9394(12)00003-7[pii]10.1016/j.ajo.2011.12.013
  • Peer Reviewed
• [Journal Article] Relationship between retinal morphological findings and visual function in age-related macular degeneration (2012)
  • Author(s): Akagi-Kurashige Y, Tsujikawa A, Oishi A, Ooto S, Yamashiro K, Tamura H, Nakata I, Ueda-Arakawa N, Yoshimura N
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: (in press)
  • DOI: 10.1007/s00417-012-1928-5
  • Peer Reviewed
• [Journal Article] Significance of C2/CFB variants in age-related macular degeneration and polypoidal choroidal vasculopathy in a Japanese population (2012)
  • Author(s): Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, Akagi-Kurashige Y, Tsujikawa A, Otani A, Saito M, Iida T, Oishi A, Matsuo K, Tajima K, Matsuda F, Yoshmura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Pages: 794-798
  • DOI: iovs.11-8468[pii]10.1167/iovs.11-8468
  • Peer Reviewed
• [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: 151 Pages: 961-972
• [Journal Article] Association of elastin gene polymorphism to age-related nacular degeneration and polypoidal choroidal vasculopathy (2011)
  • Author(s): Yamashiro K, Mori K, Nakata I, Tsuchihashi T, Horie-Inoue K, Nakanishi H, Tsujikawa A, Saito M, Iida T, Yamada R, Matsuda F, Inoue S, Awata T, Yoneya S, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 8780-8784
  • DOI: 10.1167/iovs.11-8205
  • Peer Reviewed
• [Journal Article] Treatment of polypoidal choroidal vasculopathy with photodynamic therapy combined with intravitreal injections of ranibizumab (2011)
  • Author(s): Tomita K, Tsujikawa A, Yaiashiro K, Ooto S, Tamura H, Otani A, Nakayana Y, Yoshimura N
  • Journal Title: Am J Ophthalmol Volume: 153 Pages: 68-80
  • DOI: S0002-9394(11)00546-0[pii]10.1016/j.ajo.2011.07.001
  • Peer Reviewed
• [Journal Article] VEGF gene polymorphism and response to intravitreal bevacizumab and triple therapy in age-related macular degeneration (2011)
  • Author(s): Nakata I, Yamashiro K, Nakanishi H, Tsujikawa A, Otani A, Yoshimura N
  • Journal Title: Jpn J Ophthalmol Volume: 55 Pages: 435-443
  • DOI: 10.1007/s10384-011-0061-z
  • Peer Reviewed
• [Journal Article] Macular choroidal thickness and volume in normal subjects measured by swept-source optical coherence tomography (2011)
  • Author(s): Hirata M, Tsujikawa A, Matsumoto A, Hangai M, Ooto S, Yamashiro K, Akiba M, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 4971-4978
  • DOI: iovs.11-7729[pii]10.1167/iovs.11-7729
  • Peer Reviewed
• [Journal Article] Association between the SERPING1 gene and age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese (2011)
  • Author(s): Nakata I, Yamashiro K, Yamada R, Gotoh N, Nakanishi H, Hayashi H, Tsujikawa A, Otani A, Saito M, Iida T, Oishi A, Matsuo K, Tajima K, Matsuda F, Yoshimura N
  • Journal Title: PLoS One Volume: 6 Pages: e19108
  • DOI: 10.1371/journal.pone.0019108
  • 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: 118 Pages: 1408-1415
  • DOI: S0161-6420(10)01304-7[pii]10.1016/j.ophtha.2010.12.011
  • 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, Yanada R, Matsuda F, Yoshimura N
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Pages: 4853-4858
  • DOI: iovs.11-7311[pii]10.1167/iovs.11-7311
  • Peer Reviewed