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2014 Fiscal Year Annual Research Report

HLA-Aアリルの東アジアにおけるベーチェット病遺伝要因としての意義に関する研究

Research Project

Project/Area Number 23406031
Research InstitutionThe University of Tokyo

Principal Investigator

竹内 二士夫  東京大学, 医学部附属病院, 講師 (70154979)

Co-Investigator(Kenkyū-buntansha) 桑田 昇治  帝京大学, 医学部, 教授 (00241993)
蕪城 俊克  東京大学, 医学部附属病院, 講師 (00280941)
針原 伸二  東京大学, 理学(系)研究科(研究院), 助教 (40198932)
萩野 昇  帝京大学, 医学部, 講師 (40466769)
野口 博司  静岡県立大学, 薬学部, 教授 (60126141)
Project Period (FY) 2011-04-01 – 2015-03-31
Keywordsベーチェット病 / 国際情報交換 / 東アジア / 疾患感受性遺伝子 / HLA / IL23R / 3次元構造 / 民族差
Outline of Annual Research Achievements

本研究はベーチェット病(BD)におけるHLAの遺伝因子としての意義を検討するとともに、その民族差、IL23Rとの関連を検討し、遺伝的背景を解明する事を目的とする。有病率は韓国、米国の情報では各々33.8/100000、5.2だった。タイチェンマイ大の患者数はRA、SLE、SSCの各3,3,10%であり、東大での各15,45,129%と比べて少なかった。日本の検体は正常(C)213、BD総計170を得、HLAを検討した。IL23Rも分析したBD136例の集計では、A*0207はA*2601及びB*5101陰性群(両陰性群)でOR=2.82(95%CI=1.01-7.85)の有意な相関を認めた。タイではC 99、BD 26検体のHLAを分析した。BDでは、両陰性群でA*0207は表現型頻度(PF)が52.9%とCの27.3%と比べて有意に増加していた(p<0.05)。 台湾のBDでもA*0207が増加していたが(PF=36.4%)が有意差を得られなかった。これらの結果はA*0207が東アジアにおけるBDの第3の感受性遺伝子である事を示唆すると考えられる。A*2601はタイBDでは遺伝子頻度(AF)=3.8%で相関がみられなかったが、Cでも1.5%と低かった。B*5101の頻度も日本、韓国と比べて低値であり、BDの有病率が低い事の遺伝的要因になっていると考えられる。台湾でも同様の傾向であった。臨床所見ではA*2601陽性群では前部ぶどう膜炎症例が少なく、汎ぶどう膜炎が多い傾向がみられた(P=0.0591)。IL23R-IL12RB領域のSNPの検討ではrs1495966*AがHLAと独立して相関し(p<0.05)、日本とタイで民族差があった。HLAとMICA-TM(AAAAAIFVI)との結合の自由エネルギー計算では、相関するHLAは7-11Kcal/mol強く結合していた。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

  • Research Products

    (33 results)

All 2015 2014

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 1 results) Presentation (17 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Distribution of HLA-DR alleles among Thai patients with rheumatpid arthritis.2015

    • Author(s)
      Louthrenoo W, Kasitanon N, Wangkaew S, Kuwata S, Takeuchi F
    • Journal Title

      Hum Immunol

      Volume: 76 Pages: 113-117

    • DOI

      10.1016/j.humimm.2015.01.018

    • Peer Reviewed
  • [Journal Article] Investigation of Japanese-specific alleles: Most are of Jomon lineage2015

    • Author(s)
      Yuasa I, Umetsu K, Adachi N, Matsusue A, Nakayashiki N, Fujihara J, Akane A, Harihara S, Jin F, Ishikawa T
    • Journal Title

      Leg Med (Tokyo)

      Volume: 17 Pages: 52-55

    • DOI

      10.1016/j.legalmed.2014.08.006

    • Peer Reviewed
  • [Journal Article] Statistical analyses of Endogenous Uveitis Patients (2007-2009) in central Tokyo area and Comparison with Previous Studies (1963-2006)2014

    • Author(s)
      Nakahara H, Kaburaki T, Takamoto M, Okinaga K, Matsuda J, Konno Y, Kawashima H, Numaga J, Fujino Y, Amano S.
    • Journal Title

      Ocul Immunol Inflamm

      Volume: 25 Pages: 1-6

    • Peer Reviewed
  • [Journal Article] Temporal changes in a giant macular hole formed secondary to toxoplasmic retinochoroiditis2014

    • Author(s)
      Tanaka R, Obata R, Sawamura H, Ohtomo K, Kaburaki T
    • Journal Title

      Can J Ophthalmol

      Volume: 49 Pages: e115-118

    • DOI

      10.1016/j.jcjo.2014.06.006

    • Peer Reviewed
  • [Journal Article] Evaluation of the Long-Term Efficacy and Safety of Infliximab Treatment for Uveitis in Behçet's Disease: A Multicenter Study2014

    • Author(s)
      Takeuchi M, Kezuka T, Sugita S, Keino H, Namba K, Kaburaki T, Maruyama K, Nakai K, Hijioka K, Shibuya E, Komae K, Hori J, Ohguro N, Sonoda KH, Mizuki N, Okada AA, Ishibashi T, Goto H, Mochizuki M
    • Journal Title

      Ophthalmology

      Volume: 121 Pages: 1877-1884

    • DOI

      10.1016/j.ophtha.2014.04.042

    • Peer Reviewed
  • [Journal Article] Ocular Behçet Disease Research Group of Japan. Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab2014

    • Author(s)
      Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N
    • Journal Title

      Jpn J Ophthalmol

      Volume: 58 Pages: 120-130

    • DOI

      10.1007/s10384-013-0294-0

    • Peer Reviewed
  • [Journal Article] Bilateral endogenous Candida albicans subretinal abscess with suspected mixed bacterial infection2014

    • Author(s)
      Arai Y, Sato Y, Yoshida A, Kawashima H, Kaburaki T, Gomi H
    • Journal Title

      Clin Ophthalmol

      Volume: 21 Pages: 2151-2155

    • DOI

      10.2147/OPTH.S70289

    • Peer Reviewed
  • [Journal Article] Non-Heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids2014

    • Author(s)
      Ishikawa N, Tanaka H, Koyama F, Noguchi H, Wang C C C, Hotta K, Watanabe K
    • Journal Title

      Angew. Chem Int Ed

      Volume: 53 Pages: 12880-12884

    • DOI

      10.1002/anie.201407920

    • Peer Reviewed
  • [Journal Article] Elucidation of Pseurotin Biosynthetic Pathway Points to Trans-Acting C-Methyltransferase: Generation of Chemical Diversity2014

    • Author(s)
      Tsunematsu Y, Fukutomi M, Saruwatari T, Noguchi H, Hotta K, Tang Y, Watanabe K
    • Journal Title

      Angew. Chem. Int. Ed

      Volume: 53 Pages: 8475-8479

    • DOI

      10.1002/anie.201404804

    • Peer Reviewed
  • [Journal Article] Effect of miroestrol on ovariectomy-induced cognitive impairment and lipid peroxidation in mouse brain2014

    • Author(s)
      Monthakantirata O, Sukanoa W, Umehara K, Noguchi H, Chulikhita Y, Matsumoto K
    • Journal Title

      Phytomedicine

      Volume: 21 Pages: 1249-1255

    • DOI

      10.1016/j.phymed.2014.06.012

    • Peer Reviewed
  • [Journal Article] Cytochrome P450 as Dimerization Catalyst in Diketopiperazine Alkaloid Biosynthesis2014

    • Author(s)
      Saruwatari T, Yagishita F, Mino T, Noguchi H, Hotta K, Watanabe K
    • Journal Title

      ChemBioChem

      Volume: 15 Pages: 656-659

    • DOI

      10.1002/cbic.201300751

    • Peer Reviewed
  • [Journal Article] Cytotoxic and immunomodulatory effects of polyhydroxyoctane isolated from Lentinus polychrous mycelia2014

    • Author(s)
      Fangkrathok N, Junlatat J, Umehara K, Noguchi H, Sripanidkulchai B
    • Journal Title

      J. Nat. Med

      Volume: 68 Pages: 302-309

    • DOI

      10.1007/s11418-013-0797-5

    • Peer Reviewed
  • [Journal Article] Identification of a new angiotensin-converting enzyme (ACE) inhibitor from Thai edible plants2014

    • Author(s)
      Simaratanamongkol A, Umehara K, Noguchi H, Panichayupakaranant P
    • Journal Title

      Food Chemistry

      Volume: 165 Pages: 92-97

    • DOI

      10.1016 /j.foodchem.2014.05.080

    • Peer Reviewed
  • [Journal Article] Angiotensin-converting enzyme (ACE) inhibitory activity of Solanum torvum and isolation of a novel methyl salicylate glycoside2014

    • Author(s)
      Simaratanamongkol A, Umehara K, Noguchi H, Panichayupakaranant P
    • Journal Title

      J. of Functional Foods

      Volume: 11 Pages: 557-562

    • DOI

      10.1016/j.jff.2014.08.014

    • Peer Reviewed
  • [Journal Article] Structure and Antioxidant Activity Relationships of Isoflavonoids from Dalbergia parviflora2014

    • Author(s)
      Promden W, Monthakantirat O, Umehara K, Noguchi H, De-Eknamkul W
    • Journal Title

      Molecules

      Volume: 19 Pages: 2226-2237

    • DOI

      10.3390/molecules19022226

    • Peer Reviewed / Open Access
  • [Presentation] The two Japanese ancestral groups, Jomon and Yayoi peoples -Forum the perspective of mitochondrialDNA and Y chromosomal DNA polymorphisms2014

    • Author(s)
      Sumi, H, Sato Y, Harihara S
    • Organizer
      Forum for Anthropology and Paleopathology in East Asia
    • Place of Presentation
      早稲田大学(東京都・新宿区)
    • Year and Date
      2014-11-27 – 2014-11-27
  • [Presentation] MICA-TM peptide selectively bind to HLAs associated with Behcet’s disease2014

    • Author(s)
      Kongkaew S, Yodmanee P, Kaiyawet N, Meeprasert A, Rungrotmongkol T, Kaburaki T, Noguchi H, Takeuchi F, Kungwan N, Hannongbua S
    • Organizer
      XII International Conference on Bioinformatics, Computational Biology and Biomedical Engineering, Kyoto
    • Place of Presentation
      京都ブライトンホテル (京都府・京都市)
    • Year and Date
      2014-11-13 – 2014-11-14
  • [Presentation] Estrogenic/ anti-estrogenic constituents from Bangladesh medicinal plant, Pothos scandens.2014

    • Author(s)
      Md. Abdul Muhit, Kaoru Umehara, Hiroshi Noguchi
    • Organizer
      11th Japan-China International Symposium on Health Sciences (Shizuoka)
    • Place of Presentation
      日本平ホテル(静岡県・静岡市)
    • Year and Date
      2014-11-06 – 2014-11-06
  • [Presentation] タイ薬用植物由来イソフラボノイドの抗デング熱作用2014

    • Author(s)
      梅原 薫、左 一八、安倍智子、Orawan Monthakantirat、Wanchai De-Eknamkul、Noorsaadah Abd. Rahman、 鈴木 隆、野口博司
    • Organizer
      第20回天然薬物の開発と応用シンポジウム
    • Place of Presentation
      東京大学(東京都・文京区)
    • Year and Date
      2014-11-06 – 2014-11-06
  • [Presentation] 母方先祖には先住民が、父方先祖には外来の権力民が現れる例;日本人平均と飛騨びと -DNA解析より-2014

    • Author(s)
      住 斉、佐藤陽一、針原伸二
    • Organizer
      第68回日本人類学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県・浜松市)
    • Year and Date
      2014-11-01 – 2014-11-01
  • [Presentation] 9世紀の太政官令『飛騨の民の顔付は他国と違う』を裏打ちする状況;7世紀人骨と現代人DNAより2014

    • Author(s)
      住 斉、田中和彦、佐藤陽一、針原伸二
    • Organizer
      第68回日本人類学会大会
    • Place of Presentation
      アクトシティ浜松(静岡県・浜松市)
    • Year and Date
      2014-11-01 – 2014-11-01
  • [Presentation] Relationship of Behet disease ocular attack score 24 and visual prognosis in patients with Behҫet disease2014

    • Author(s)
      Toshikatsu Kaburaki, Rie Tanaka, Mitsuko Takamoto, Kimiko Okinaga, Keiko Komae, Junko Matsuda, Jiro Numaga, Yujiro Fujino
    • Organizer
      16th International congress of Behcet disease
    • Place of Presentation
      Paris (France)
    • Year and Date
      2014-09-18 – 2014-09-18
  • [Presentation] Anti Dengue and Leishmanicidal Activities of Flavonoids from Thai Medicinal plants2014

    • Author(s)
      Kaoru Umehara, Tomoko Abe, Kazuya Hidari, Takashi Suzuki, Kanami Mori-Yasumoto, Setsuko Sekita, Orawan Monthakantirat, Wanchai De-Eknamkul, Hiroshi Noguchi
    • Organizer
      27th International Conference on Polyphenol
    • Place of Presentation
      名古屋大学(愛知県・名古屋市)
    • Year and Date
      2014-09-02 – 2014-09-06
  • [Presentation] 不明熱2014

    • Author(s)
      萩野昇
    • Organizer
      米国内科学会(ACP)日本支部学術集会
    • Place of Presentation
      京都大学(京都府・京都市)
    • Year and Date
      2014-05-31 – 2014-06-01
  • [Presentation] Structure function relationship of type III polyketide synthase2014

    • Author(s)
      Hiroshi Noguchi
    • Organizer
      The 3rd Current Drug Development International Conference
    • Place of Presentation
      Ao Nang (タイ)
    • Year and Date
      2014-05-01 – 2014-05-03
    • Invited
  • [Presentation] Intraocular NK/T cell Lymphoma Masquerading As Acute Uveitis2014

    • Author(s)
      Megumi Kobayashi, Toshikatsu Kaburaki, Hideki Tsuji
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] Reasons of the Application of Infliximab Therapy to the Patients with Ocular Behçet's Disease2014

    • Author(s)
      Toshikatsu Kaburaki, Kenichi Namba, Koh-hei Sonoda, Takeshi Kezuka, Hiroshi Keino
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] Primary Care for Patients with Uveitis(Learning From Clinical Uveitic Cases“Case 3”2014

    • Author(s)
      Toshikatsu Kaburaki
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] Frequencies of retinal arteritis and phlebitis in the patients with infectious uveitis2014

    • Author(s)
      Hisako Ono, Toshikatsu Kaburaki, Kazuyoshi Otomo, Junko Matsuda, Yujiro Fujino
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] Infliximab trough levels and anti-infliximab antibody in patients of Behcet's disease receiving infliximab2014

    • Author(s)
      Aya Matsuda, Toshikatsu Kaburaki, Kimiko Okinaga, Yujiro Fujino, Keiko Komae, Hidetoshi Kawashima
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] Frequencies of uveitis in Central Tokyo area (2010-2012)2014

    • Author(s)
      Hisae Nakahara, Toshikatsu Kaburaki, Rie Tanaka, Jiro Numaga
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Presentation] A case of bilateral endogenous Candida albicans subretinal abscess suspected to have a mixed infection with bacteria2014

    • Author(s)
      Yusuke Arai, Yukihiro Sato, Atsushi Yoshida, Hidetoshi Kawashima, Toshikatsu Kaburaki
    • Organizer
      World Ophthalmology Congress (WOC) 2014 in TOKYO
    • Place of Presentation
      東京国際フォーラム(東京都・千代田区)
    • Year and Date
      2014-04-09 – 2014-04-09
  • [Book] 学んでみると遺伝学はおもしろい2014

    • Author(s)
      針原伸二
    • Total Pages
      224
    • Publisher
      ベレ出版

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Published: 2016-06-10  

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