| Project/Area Number |
22590524
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
KOJIMA Tetsuhito 名古屋大学, 医学系研究科(保健), 教授 (40161913)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUSHITA Tadashi 名古屋大学, 医学部附属病院, 教授 (30314008)
TAKAGI Akira 名古屋大学, 大学院・医学系研究科(保健), 助教 (30135371)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 臨床血液学 / 静脈血栓塞栓症 / 先天性血栓性素因 / 遺伝子変異 / アンチトロンビン抵抗性 / 原因遺伝子変異 / ｱﾝﾁﾄﾛﾝﾋﾞﾝ欠損症 / ﾌﾟﾛﾃｲﾝC欠損症 / ﾌﾟﾛﾃｲﾝS欠損症 / ｱﾝﾁﾄﾛﾝﾋﾞﾝ抵抗性 / ｽｸﾘ―ﾆﾝｸﾞ検査法 / アンチトロンビン欠損症 / プロテインC欠損症 / プロテインS欠損症 / スクリーニング検査法 |
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| Research Abstract |
Venous thromboembolism is a multifactorial disease resulting from a complex interaction between circumstantial and genetic factors. In this study, we investigated possible causative gene defects in a large Japanese family with inherited thrombophilia, and found a novel missense mutation in the prothrombin gene resulting in a variant prothrombin. The mutation located at one of the antithrombin (AT) binding sites of thrombin molecule. We prepared wild-type and mutant recombinant prothrombins, and compared by prothrombin activation, AT-binding, and thrombin generation assays. In thrombin-antithrombin complex (TAT) formation, the mutant thrombin was impareded to form TAT. In thrombin generation assay of reconstituted prothrombin-deficient plasma with recombinant prothrombins, the mutant showed a decreased peak thrombin and an increased endogenous thrombin potential. We identified a novel F2 mutation leading to the mutant AT-resistant thrombin, which could be a cause of the inherited thrombophilia in this family.
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