Studies on thrombotic risk of protein S K196E mutation
Project/Area Number |
16K09834
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | National Cardiovascular Center Research Institute |
Principal Investigator |
Miyata Toshiyuki 国立研究開発法人国立循環器病研究センター, 病院, 非常勤研究員 (90183970)
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Co-Investigator(Kenkyū-buntansha) |
吉松 淳 国立研究開発法人国立循環器病研究センター, 病院, 部長 (20221674)
秋山 正志 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30298179)
丸山 慶子 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (30712624)
小亀 浩市 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (40270730)
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Research Collaborator |
Akiyama Masashi 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30298179)
Maruyama Keiko 国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (30712624)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 静脈血栓塞栓症 / プロテインS / 凝固制御因子 / 遺伝子変異 / 経口避妊薬 / 血栓性素因 / 静脈血栓症、 / 変異体 / 静脈血栓症 |
Outline of Final Research Achievements |
We have previously reported that the mutation of protein S p.Lys196Glu (PS K196E) is a Japanese-specific genetic risk factor for venous thromboembolism. We expressed recombinant human protein S wild-type (PS-K) and K196E-mutant (PS-E) in CHO cells. PS-E had approximately 40% activated protein C cofactor activity compared with PS-K. The tissue factor pathway inhibitor cofactor activity of PS-E was equivalent to that of PS-K. The strengths of PS-E and PS-K binding to the beta-chain of C4b binding protein were comparable. Therefore, the PS K196E mutation increases the risk of venous thromboembolism because of reduced activated protein C cofactor activity. We identified a patient with cerebral venous thrombosis who had the PS K196E mutation. We identified 6 PS K196E carriers with combined oral contraceptive use.
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Academic Significance and Societal Importance of the Research Achievements |
私達はプロテインS p.Lys196Glu (PS K196E) 変異は日本人の静脈血栓塞栓症の遺伝的リスク(性と年齢で調整したオッズ比4.72)であることを報告してきた。本変異はこれまで日本人にのみ見られ中国人や韓国人にも同定されていないので、本邦で研究を進める必要がある。PS K196E変異体は活性化プロテインCの補酵素活性が約40%低下するという今回の結果は、変異体保有者のPS抗凝固活性の低下を説明するものである。
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Report
(4 results)
Research Products
(51 results)
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[Journal Article] Effects of low-dose combined oral contraceptives and protein S K196E mutation on anticoagulation factors: a prospective observational study2019
Author(s)
Takekazu Miyoshi, Hisato Oku, Saiko Asahara, Akira Okamoto, Koichi Kokame, Michikazu Nakai, Kunihiro Nishimura, Fumiyuki Otsuka, Aya Higashiyama, Jun Yoshimatsu, Toshiyuki Miyata
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Journal Title
International Journal of Hematology
Volume: 印刷中
Issue: 6
Pages: 641-649
DOI
Related Report
Peer Reviewed
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[Journal Article] The international hereditary thrombotic thrombocytopenic purpura (TTP) registry: Key findings at enrolment until 20172019
Author(s)
van Dorland HA, Mansouri Taleghani M, Sakai K, Friedman KD, George JN, Hrachovinova I, Knobl PN, von Krogh AS, Schneppenheim R, Aebi-Huber I, Butikofer L, Largiader CR, Cermakova Z, Kokame K, Miyata T, Yagi H, Terrell DR, Vesely SK, Matsumoto M, Lammle B, Fujimura Y, Kremer Hovinga JA
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Journal Title
Haematologica
Volume: 印刷中
Issue: 10
Pages: 2107-2115
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] von Willebrand factor aggravates hepatic ischemia-reperfusion injury by promoting neutrophil recruitment in mice2018
Author(s)
Urisono Y, Sakata A, Matsui H, Kasuda S, Ono S, Nishio K, Sho M, Okuchi K, Akiyama M, Miyata T, Nishimura S, Sugimoto M
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Journal Title
Thromb Haemost
Volume: 118
Issue: 04
Pages: 700-708
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical manifestation of patients with atypical hemolytic uremic syndrome with the C3 p.I1157T variation in the Kinki region of Japan.2018
Author(s)
Matsumoto T, Toyoda H, Amano K, Hirayama M, Ishikawa E, Fujimoto M, Ito M, Ohishi K, Katayama N, Yoshida Y, Matsumoto M, Kawamura N, Ikejiri M, Kawakami K, Miyata T, Wada H
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Journal Title
Clin Appl Thromb Hemost
Volume: 24
Issue: 8
Pages: 1301-1307
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clinical manifestation of atypical hemolytic uremic syndrome patients with the C3 p.I1157T variation in the Kinki region of Japan2018
Author(s)
Matsumoto T, Toyoda, H, Amano K, Hirayama M, Ishikawa E, FujimotoM, Ito M, Ohishi, K, Katayama N, Yoshida Y, Matsumoto M, Kawamura N, Ikejiri M, Kawakami K, Miyata T, Wada H
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Journal Title
Clin Appl Thromb Hemost
Volume: 印刷中
Related Report
Peer Reviewed
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[Journal Article] For TTP group of Blood Coagulation Abnormalities Research Team, Research on Rare and Intractable Disease supported by Health, Labour, and Welfare Sciences Research Grants.: Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) 2017 in Japan.2017
Author(s)
Matsumoto M, Fujimura Y, Wada H, Kokame K, Miyakawa Y, Ueda Y, Higasa S, Moriki T, Yagi H, Miyata T, Murata M;
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Journal Title
Int J Hematol
Volume: 106
Issue: 1
Pages: 3-15
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Influence of a rotational speed modulation system used with an implantable continuous-flow left ventricular assist device (EVAHEART) on von Willebrand factor dynamics2016
Author(s)
Noritsugu Naito, Toshihide Mizuno, Takashi Nishimura, Satoru Kishimoto, Yoshiaki Takewa, Yuka Eura, Koichi Kokame, Toshiyuki Miyata, Kazuma Date, Akihide Umeki, Masahiko Ando, Minoru Ono, and Eisuke Tatsumi
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Journal Title
Artif. Organs
Volume: 未定
Issue: 9
Pages: 877-883
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Disease Recurrence After Early Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome With Complement C3 I1157T Mutation.2016
Author(s)
Toyoda, H., Wada, H., Miyata, T., Amano, K., Kihira, K., Iwamoto, S., Hirayama, M., Komada, Y.
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Journal Title
J Pediatr Hematol Oncol
Volume: 38
Issue: 3
Pages: e137-e139
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Book] 臨床脈管学2017
Author(s)
宮田敏行、辻明宏
Total Pages
2
Publisher
日本医学出版
ISBN
9784865770278
Related Report