| Project/Area Number |
17K11245
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nagoya City University |
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Principal Investigator |
Katano Kinue 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (90305524)
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| Co-Investigator(Kenkyū-buntansha) |
杉浦 真弓 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30264740)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 抗リン脂質抗体症候群 / 不育症 / TSHR / C1D / ダナパロイド / アスピリン / 未分画ヘパリン / 習慣流産 / ゲノムワイド関連解析 / 国際共同研究 |
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| Outline of Final Research Achievements |
Antiphospholipid syndrome (APS) is one of the causes of recurrent pregnancy loss. We found new susceptibility loci in TSHR, C1D, NGF, SYCP2L, HLA-DRA, GATA3, FRMD4A, PTPRO for APS with the use of genome-wide association study. We examined 14 patients with APS and now continue to collect samples and analyze.
Combination of low dose aspirin and unfractionated heparin (UFH) is a standard treatment for APS. Danaparoid has a fewer side effects such as bleeding, heparin induced thrombocytopenia (HIT) and osteoporosis. We examined 91 pregnancies of 60 patients with APS. After excluding 11 miscarriages with abnormal embryonic chromosomes, one chemical pregnancy and one ectopic pregnancy, live birth rates were 87.5 % for the danaparoid group, 90.0% for the UFH group and 63.6 % for the LDA group, respectively. No patient given danaparoid and one patient with UFH developed HIT. Danaparoid is effective for improving the live birth rate and is safe for patients with APS.
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| Academic Significance and Societal Importance of the Research Achievements |
抗リン脂質抗体症候群は抗凝固療法により70－80％が出産できるが、20-30%は流死産となり、若年性脳梗塞を起こす難治性疾患である。関連遺伝子が明らかになれば新たな分子標的薬の開発が期待できる。
現在の抗凝固療法は未分画ヘパリンが用いられているが、出血、ヘパリン惹起性血小板減少症、骨粗鬆症の副作用が問題となる。ダナパロイドはこれらの副作用が少ないことがわかっているが、出産率改善の効果は本研究によって世界で初めて明らかになった。一日一回の自己注射が保険適用されれば患者の利便性が高まる。
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