血漿ｓＦｌｔ１／ＰｌＧＦ比の妊娠高血圧腎症発症域値を用いた予知法の開発

2014 Fiscal Year Research-status Report

• Project/Area Number: 24592482
• Research Institution: Jichi Medical University
• Principal Investigator: 大口 昭英 自治医科大学, 医学部, 准教授 (10306136)
• Project Period (FY): 2012-04-01 – 2017-03-31
• Keywords: 妊娠高血圧腎症

Outline of Annual Research Achievements

平成24年4月～平成27年3月にかけて983件のコホート採血をした（妊娠20～37週：重複あり）．そのうち，平成25年12月までのハイリスク妊婦コホート156例について，ELISA法によるsFlt-1, PlGFを測定した．
平成16年～平成20年にかけて収集した第１次コホートでは，妊娠26～31週での妊婦採血数が784例であったので，本年度での採血により，validation研究としては十分な数の症例するが集積したと考えた．
次年度以降，ハイリスク妊婦について，引き続きsFlt-1，PlGFを測定し，最終年度に，sFlt-1/PlGF比を用いたimminent onset of PE発症予知のexternal checkを行う予定である．

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

第一次コホート（784例）に見合うだけの新規コホート（983例）に対して試料を収集することができた．

Strategy for Future Research Activity

研究開始後，33か月で，983件の試料が集まった．当初，5年間で1500例のコホートを集積することが目的であったが，第1次コホート（平成12～16年）での妊娠26～31週での採血数784例に相当する採血が集まったため，本年4月を持って，試料の収集を終了することにした．
今後は，研究資金が入り次第，ハイリスク妊婦の試料について，引き続き，sFlt-1, PlGFを測定してゆき，最終年度に，external validationのための解析を行う予定である．

Causes of Carryover

次年度で，sFlt-1, PlGFを測定するため．

Expenditure Plan for Carryover Budget

本年度，ハイリスク妊婦の試料について，sFlt-1, PlGFを測定する．

Research Products

• [Journal Article] Maternal peripheral blood natural killer cells incorporate placenta-associated microRNAs during pregnancy. (2015)
  • Author(s): Ishida Y, Zhao D, Ohkuchi A, Kuwata T, Yoshitake H, Yuge K, Takizawa T, Matsubara S, Suzuki M, Saito S, Takizawa T.
  • Journal Title: Int J Mol Med Volume: 35 Pages: 1511-1524
  • DOI: 10.3892/ijmm.2015.2157.
  • Peer Reviewed
• [Journal Article] A novel three-step approach for predicting the imminent onset of preeclampsia within 4 weeks after blood sampling at 19-31 weeks of gestation. (2014)
  • Author(s): Hirashima C, Ohkuchi A, Takahashi K, Suzuki H, Matsubara S, Suzuki M.
  • Journal Title: Hypertens Res Volume: 37 Pages: 519-525
  • DOI: 10.1038/hr.2014.31.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition. (2014)
  • Author(s): Minakami H, Maeda T, Fujii T, Hamada H, Iitsuka Y, Itakura A, Itoh H, Iwashita M, Kanagawa T, et al.
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Pages: 1469-1499
  • DOI: 10.1111/jog.12419.
  • Peer Reviewed
• [Journal Article] Differential expression of ADAM (a disintegrin and metalloproteinase) genes between human first trimester villous and extravillous trophoblast cells. (2014)
  • Author(s): Takahashi H, Yuge K, Matsubara S, Ohkuchi A, Kuwata T, Usui R, Suzuki M, Takizawa T.
  • Journal Title: J Nippon Med S Volume: 81 Pages: 122-129
  • Peer Reviewed
• [Journal Article] Human exosomal placenta-associated miR-517a-3p modulates the expression of PRKG1 mRNA in Jurkat cells. (2014)
  • Author(s): Kambe S, Yoshitake H, Yuge K, Ishida Y, Ali MM, Takizawa T, Kuwata T, Ohkuchi A, Matsubara S, Suzuki M, Takeshita T, Saito S, Takizawa T.
  • Journal Title: Biol Reprod Volume: 91 Pages: 129
  • DOI: 10.1095/biolreprod.114.121616.
  • Peer Reviewed
• [Journal Article] Recurrence Risk of Hypertensive Disease in Pregnancy (2014)
  • Author(s): Kayo Takahashi, Akihide Ohkuchi, Mami Kobayashi, Shigeki Matsubara, and Mitsuaki Suzuki
  • Journal Title: Med J Obset Gynecol Volume: 2 Pages: 1023
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prediction of Early-Onset Preeclampsia Using Uterine Artery Doppler (2014)
  • Author(s): Akihide Ohkuchi, Kayo Takahashi, Chikako Hirashima, RieUsui, Shigeki Matsubara and Mitsuaki Suzuki
  • Journal Title: Med J Obset Gynecol Volume: 2 Pages: 1026
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prediction of Early-Onset Preeclampsia Using Angiogenesis-Related Factors (2014)
  • Author(s): Chikako Hirashima, Akihide Ohkuchi, Kayo Takahashi, Rie Usui, Shigeki Matsubara and Mitsuaki Suzuki
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1025
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Risk of Preeclampsia in Women with CKD, Dialysis or Kidney Transplantation (2014)
  • Author(s): Noriko Hirose, Akihide Ohkuchi, RieUsui, Shigeki Matsubara, and Mitsuaki Suzuki
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1028
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Risk Factors Associated with the Occurrence of Preeclampsia in Women with Twin Pregnancies: Mini Review (2014)
  • Author(s): Akihide Ohkuchi
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1027
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The Role of the Father in the Occurrence of Preeclampsia (2014)
  • Author(s): Shiho Nagayama, Akihide Ohkuchi, RieUsui, Shigeki Matsubara, and Mitsuaki Suzuki
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Animal Models of Preeclampsia: Insight into Possible Biomarker Candidates for Predicting Preeclampsia (2014)
  • Author(s): Hirotada Suzuki, Akihide Ohkuchi, Koumei Shirasuna, Hironori Takahashi, Rie Usui, Shigeki Matsubara and Mitsuaki Suzuki
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1031
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Importance of Chromosome 19 miRNA Cluster in Pregnancy (2014)
  • Author(s): Hironori Takahashi, Akihide Ohkuchi, Rie Usui, Toshihiro Takizawa, Shigeki Matsubara and Mitsuaki Suzuki
  • Journal Title: Med J Obstet Gynecol Volume: 2 Pages: 1032
  • Peer Reviewed
• [Journal Article] Increased antiangiogenetic factors in severe proteinuria without hypertension in pregnancy: is kidney biopsy necessary? (2014)
  • Author(s): Ohmaru T, Ohkuchi A, Muto S, Hirashima C, Matsubara S, Suzuki M
  • Journal Title: CEN Case Rep Volume: 3 Pages: 86-89
  • DOI: 10.1007/s13730-013-0092-z
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 妊娠高血圧症候群と血管新生関連因子 (2014)
  • Author(s): 大口昭英，鈴木寛正，平嶋周子，高橋佳代，松原茂樹，鈴木光明
  • Organizer: 第29回日本生殖免疫学会総会・学術集会
  • Place of Presentation: 伊藤国際学術研究センター
  • Year and Date: 2014-12-12 – 2014-12-12
• [Presentation] Decreased circulating levels of galectin-1 in the second trimester as an independent risk factor for not only preeclampsia but also gestational hypertension. (2014)
  • Author(s): Ohkuchi A, Hirashima C, Nagayama S, Suzuki H, Takahashi K, Matsubara S, Suzuki M.
  • Organizer: XIX International society for the study of hypertension in pregnancy (ISSHP) World Congress
  • Place of Presentation: Hilton – New Orleans Riverside
  • Year and Date: 2014-10-26 – 2014-10-29
• [Presentation] 妊娠中の自由行動下血圧指標はSmall for Gestational Ageに関連している． (2014)
  • Author(s): 江口和男, 大丸貴子, 大口昭英, 平嶋周子, 高橋佳代, 鈴木寛正, 苅尾七臣, 松原茂樹, 鈴木光明
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] 妊娠中期、後期前半のsFlt-1/PIGF比、及び、soluble endoglinによる妊娠高血圧腎症発症リスク評価 (2014)
  • Author(s): 平嶋周子, 大口昭英, 高橋佳代, 松原茂樹, 鈴木光明
  • Organizer: 第35回日本妊娠高血圧学会
  • Place of Presentation: 京王プラザ
  • Year and Date: 2014-09-20 – 2014-09-20
• [Presentation] The existence of inflection point in home blood pressure monitoring at earlier gestational weeks in preeclampsia and gestational hypertension. (2014)
  • Author(s): Saruyama M, Ohkuchi A, Takahashi K, Ohmaru T, Hirashima C, Suzuki H, Matsubara S, Suzuki M.
  • Organizer: 46th International Congress on Pathophysiology of Pregnancy.
  • Place of Presentation: Keio Plaza Hotel
  • Year and Date: 2014-09-19 – 2014-09-19
• [Presentation] Prediction of preeclampsia using angiogenesis-reltaed factors or home blood pressure monitoring. (2014)
  • Author(s): Ohkuchi A, HIrashima C, Saruyama M, Takahashi K, Ohmaru T, Suzuki H, Matsubara S, Suzuki M.
  • Organizer: Workshop on the 46th International Congress on Pathophysiology of Pregnancy.
  • Place of Presentation: Keio Plaza Hotel
  • Year and Date: 2014-09-19 – 2014-09-19
• [Presentation] 妊娠高血圧症候群既往歴は、血圧高値と子宮動脈血流速度異常とは独立した妊娠高血圧腎症の危険因子である (2014)
  • Author(s): 小林真実、高橋佳代、大口昭英、鈴木寛正、有賀治子、廣瀬典子、平嶋周子、松原茂樹、鈴木光明
  • Organizer: 第66回日本産婦人科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-19 – 2014-04-19