Exploration of the genes which are responsible for the pathogenesis of Takayasu arteritis
| Project/Area Number |
26670399
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
ISOBE MITSUAKI 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (80176263)
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| Co-Investigator(Kenkyū-buntansha) |
前嶋 康浩 東京医科歯科大学, 医学部附属病院, 講師 (40401393)
江花 有亮 東京医科歯科大学, 学内共同利用施設等, 講師 (60517043)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 高安動脈炎 / 一塩基多型 / インフラマソーム / 遺伝子多型 / 転写因子 / サイトカイン |
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| Outline of Final Research Achievements |
Takayasu arteritis (TA) is an autoimmune systemic arteritis of unknown etiology. We have identified that single nucleotide polymorphisms (SNPs) of MLX gene, which encodes MLX transcription factor, was significantly associated with clinical manifestations of TA by genome-wide association study. The SNPs of MLX (rs665268) is a missense mutation of MLX that alters the Gln139 to Arg(Q139R). As Gln139 is located on the DNA binding site of MLX, we hypothesized that the mutation of Q139R on MLX, which alters the electric charge of the amino acid may enhance the formation of the MLX-DNA complex. Then, based on our experimental results, we concluded that MLX-Q139R mutation plays a crucial role in the pathogenesis of TA through facilitating inflammasome formation, which in turn promoting proliferation and adhesion ability of aorta-resident cells, a pathological manifestation seen in the aortas of TA.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Takayasu arteritis and ulcerative colitis -high concurrence ratio and genetic overlap.2015
Author(s)
Terao C, Matsumura T, Yoshifuji H, Kirino Y, Maejima Y, Kochi Y, Ogimoto A, Yamamoto M, Takahashi H, Nakayamada S, Saito K, Wada Y, Narita I, Kawaguchi Y, Yamanaka H, Ohmura K, Atsumi T, Tanemoto K, Miyata T, Kuwana M, Komuro I, Tabara Y, Ueda A, Isobe M, Mimori T, Matsuda F.
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Journal Title
Arthritis Rheumatol.
Volume: -
Issue: 8
Pages: 2226-2232
DOI
Related Report
Peer Reviewed
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[Presentation] 温故知新：高安病の今、昔2015
Author(s)
磯部光章
Organizer
第56回日本脈管学会総会（会長講演）
Place of Presentation
虎ノ門ヒルズフォーラム（東京都港区）
Year and Date
2015-10-29
Related Report
Invited
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