Establishment of a high sensitivity measurement system for soluble angiotensin IV receptor and evaluation of the utility

• Project/Area Number: 25461245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Fukui
• Principal Investigator: Konoshita Tadashi 福井大学, 医学部, 准教授 (40270954)
• Co-Investigator(Renkei-kenkyūsha): ZENIMARU YASUO 福井大学, 医学部附属病院, 特命助教 (20397269) ; FUJII MIKI 福井大学, 医学部附属病院, 病院助教 (10401978) ; IMAGAWA MICHIKO 福井大学, 医学部附属病院, 特命助教 (70464055) ; ICHIKAWA MAI 福井大学, 医学部附属病院, 医員 (30646659) ; YAMADA MIKA 福井大学, 医学部附属病院, 医員 (90646655)
• Research Collaborator: SUZUKI JINYA 医学部附属病院, 講師 (20293417) ; YAMAMOTO KATSUSHI 福井大学, 医学部附属病院, 医員 (40753950) ; NAKAYA TAKAHIRO 福井大学, 医学部附属病院, 医員 (50750353) ; SAKAI AI 福井大学, 医学部附属病院, 医員 (40750352) ; MAKINO YASUKAZU 福井大学, 医学部, 大学院生 ; SATO SATSUKI 福井大学, 医学部, 大学院生
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アンジオテンシンIV受容体 / LNPEP / IRAP / レニン－アンジオテンシン系 / 高血圧 / 糖尿病 / 糖尿病性腎症

Outline of Final Research Achievements

We had identified Angiotensin IV (AT4) receptor as a hypertension/diabetes specific gene through genetic DNA chip analysis and we had already established a measurement system for this AT4. This time we tried to improve the sensitivity of the measurement by monoclonal antibody methods and as a result we could established a next generation measurement system for AT4 with largely improved sensitivity. This measurement system would be of use for medical care of life-style related diseases.

Research Products

• [Journal Article] A Genetic Variant in the Distal Enhancer Region of the Human Renin Gene Affects Renin Expression. (2015)
  • Author(s): Makino Y, Konoshita T, Omori A, Maegawa N, Nakaya T, Ichikawa M, Yamamoto K, Wakahara S, Ishizuka T, Onoe T, Nakamura H; Genomic Disease Outcome Consortium (G-DOC) Study Investigators
  • Journal Title: PLoS One. Volume: 10(9) Issue: 9 Pages: e0137469-e0137469
  • DOI: 10.1371/journal.pone.0137469
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] レニン‐アンジオテンシン系遺伝子多型と2型糖尿病発症の関連解析 (2015)
  • Author(s): 市川麻衣，此下忠志
  • Journal Title: Angiotensin Research Volume: 12 Pages: 48-50
• [Journal Article] 高血圧症とRASバイオマーカー－特にレニン遺伝子と血漿レニン活性について－ (2015)
  • Author(s): 此下忠志，中屋隆裕，市川麻衣，山本勝司，牧野耕和
  • Journal Title: Angiotensin Research Volume: 12 Pages: 194-199
• [Journal Article] Determinants of plasma renin activity - Role of a human renin gene variant as a genetic factor. (2014)
  • Author(s): Konoshita T, Nakaya T, Sakai A, Yamada M, Ichikawa M, Sato S, Imagawa M, Fujii M, Yamamoto K, Makino Y, Arakawa K, Suzuki J, Ishizuka T, Nakamura H
  • Journal Title: Medicine Volume: 93 Issue: 29 Pages: e354-e354
  • DOI: 10.1097/md.0000000000000354
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus: a modest but significant effect of aldosterone synthase. (2014)
  • Author(s): Ichikawa M, Konoshita T, Nakaya T, Yamamoto K, Yamada M, Sato S, Imagawa M, Makino Y, Fujii M, Zenimaru Y, Arakawa K, Suzuki J, Ishizuka T, Nakamura H
  • Journal Title: Acta Diabetol Volume: 51 Issue: 4 Pages: 595-599
  • DOI: 10.1007/s00592-014-0561-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pedal Edema in a Female of RS3PE. (2014)
  • Author(s): Hattori K, Konoshita T, Wakahara S, Miyamori I
  • Journal Title: J Postgrad Med Volume: 60 Issue: 2 Pages: 211-211
  • DOI: 10.4103/0022-3859.132369
  • Peer Reviewed / Open Access
• [Journal Article] Blue Toe in a Male of Cholesterol Embolization Syndrome. (2014)
  • Author(s): Arakawa K, Konoshita T, Makino Y, Ishizuka T
  • Journal Title: Clin Med Volume: 14 Issue: 6 Pages: 688-689
  • DOI: 10.7861/clinmedicine.14-6-688
  • Peer Reviewed / Open Access
• [Journal Article] 診療の極意「その一言！」「ご家族のためにも、健康で長生きしましょう」 (2014)
  • Author(s): 此下忠志
  • Journal Title: 生活習慣病News&Views Volume: 35 Pages: 14-14
• [Journal Article] Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus: a modest but significant effect of aldosterone synthase. (2014)
  • Author(s): Ichikawa M, Konoshita T, Nakaya T, Yamamoto K, Yamada M, Sato S, Imagawa M, Makino Y, Fujii M, Zenimaru Y, Arakawa K, Suzuki J, Ishizuka T, Nakamura H
  • Journal Title: Acta Diabeto Volume: in press
  • Peer Reviewed
• [Journal Article] Angiokeratoma in a Man with Fabry Disease. (2013)
  • Author(s): Mutoh H, Konoshita T, Onoe T, Makino Y, Arakawa K, Nakamura H
  • Journal Title: Am J Med Sci Volume: 346 Issue: 4 Pages: 302-302
  • DOI: 10.1097/maj.0b013e3182639555
  • Peer Reviewed
• [Journal Article] 特集「CKDと動脈硬化」，Part4 CKDにおける高血圧治療，３．CCBの適応と限界 (2013)
  • Author(s): 此下忠志，山田実夏，市川麻衣，藤井美紀
  • Journal Title: 動脈硬化予防 Volume: 12 Pages: 50-57
• [Journal Article] 特集 エビデンスからみた降圧薬の長所と短所，カルシウム拮抗薬の長所と短所 (2013)
  • Author(s): 此下忠志，山田実夏，市川麻衣，藤井美紀
  • Journal Title: 循環器内科 Volume: 74 Pages: 345-350
• [Journal Article] 心腎血管病の予測マーカー、アルブミン尿を低下させるCa拮抗薬は何か－代表的4系統Ca拮抗薬の比較－ (2013)
  • Author(s): 此下忠志
  • Journal Title: 循環plus Volume: 13 Pages: 7-9
• [Journal Article] The Genomic Disease Outcome Consortium (G-DOC) Study Investigators : A crossover comparison of urinary albumin excretion as a new surrogate marker for cardiovascular disease among 4 types of calcium channel blockers (2011)
  • Author(s): Konoshita, T
  • Journal Title: Int.J.Cardiol. Volume: (in press) Issue: 2 Pages: 448-452
  • DOI: 10.1016/j.ijcard.2011.10.133
  • Peer Reviewed
• [Presentation] Angiotensinase A（ENPEP）遺伝子型と糖尿病性腎症の関連解析 (2015)
  • Author(s): 坂井亜衣，帰山沙織，古谷真知，中屋隆裕，山田実夏，市川麻衣，佐藤さつき，今川美智子，山本勝司，藤井美紀，銭丸康夫，鈴木仁弥，牧野耕和，石塚 全，加藤規弘，此下忠志
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: 松山
  • Year and Date: 2015-10-09
• [Presentation] メタボリックシンドロームにおけるレニン－アンジオテンシン系 (2015)
  • Author(s): 市川麻衣，浦邊真知，帰山沙織，中屋隆裕，坂井亜衣，山田実夏，佐藤さつき，今川美智子，山本勝司，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，石塚 全，此下忠志
  • Organizer: 第38回日本高血圧学会総会，
  • Place of Presentation: 松山
  • Year and Date: 2015-10-09
• [Presentation] アンジオテンシン変換酵素遺伝子型と高血圧－2型糖尿病コホートにおける関連解析 (2015)
  • Author(s): 中屋隆裕，帰山沙織，浦邊真知，坂井亜衣，山田実夏，市川麻衣，佐藤さつき，今川美智子，山本勝司，藤井美紀，銭丸康夫，鈴木仁弥，牧野耕和，石塚 全，此下忠志
  • Organizer: 第38回日本高血圧学会総会，
  • Place of Presentation: 松山
  • Year and Date: 2015-10-09
• [Presentation] N/L type calcium channel blocker, cilnidipine, leads to less elevation of plasma aldosterone compared to l type calcium channel blocker, amlodipine besilate on the top of valsartan administration. (2015)
  • Author(s): Konoshita T, Nakaya T, Sakai A, Yamada M, Ichikawa M, Yamamoto K, Sato S, Imagawa M, Makino Y, Fujii M, Zenimaru Y, Suzuki J, Ishizuka T
  • Organizer: 25th European Meeting on Hypertension
  • Place of Presentation: Milan
  • Year and Date: 2015-06-12
  • Int'l Joint Research
• [Presentation] Genetic variant of the renin-angiotensin system and prevalence of type 2 diabetes mellitus. (2015)
  • Author(s): Ichikawa M, Konoshita T, Nakaya T, Sakai A, Yamada M, Yamamoto K, Sato S, Imagawa M, Makino Y, Fujii M, Zenimaru Y, Suzuki J, Ishizuka T
  • Organizer: 25th European Meeting on Hypertension
  • Place of Presentation: Milan
  • Year and Date: 2015-06-12
  • Int'l Joint Research
• [Presentation] ENPEP（angiotensinase A）遺伝子多型と高血圧症の相関解析 (2014)
  • Author(s): 坂井亜衣，中屋隆裕，山本勝司，山田実夏，市川麻衣，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，石塚 全，ジャギデジャ ムードレイ，加藤規弘，此下忠志
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] アルドステロン合成酵素遺伝子多型と慢性腎臓病の相関解析 (2014)
  • Author(s): 中屋隆裕，坂井亜衣，山本勝司，山田実夏，市川麻衣，佐藤さつき，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，石塚 全，ジャギデジャ ムードレイ，此下忠志
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] 高齢２型糖尿病における血圧と循環レニン-アンジオテンシン系の特性 (2014)
  • Author(s): 山本勝司，中屋隆裕，坂井亜衣，山田実夏，市川麻衣，佐藤さつき，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，石塚 全，ジャギデジャ ムードレイ，此下忠志
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] レニン－アンジオテンシン系遺伝子と２型糖尿病の関連解析 (2014)
  • Author(s): 市川麻衣，中屋隆裕，坂井亜衣，山本勝司，山田実夏，佐藤さつき，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，石塚 全，ジャギデジャ ムードレイ，此下忠志
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: 横浜、パシフィコ横浜
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] Determinants of plasma renin activity – role of a human renin gene variant as a genetic factor. (2014)
  • Author(s): Konoshita T, Nakaya T, Yamamoto K, Yamada M, Ichikawa M, Sato S, Imagawa M, Makino Y, Fujii M, Zenimaru Y, Arakawa K, Suzuki J, Ishizuka T, Nakamura H
  • Organizer: 24th European Meeting on Hypertension
  • Place of Presentation: Athens, Greece
  • Year and Date: 2014-06-13 – 2014-06-16
• [Presentation] 高齢２型糖尿病症例の特徴，特に循環レニン-アンジオテンシン系について (2014)
  • Author(s): 山本勝司，中屋隆裕，山田実夏，市川麻衣，佐藤さつき，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，此下忠志
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] レニン－アンジオテンシン系遺伝子多型と２型糖尿病発症の関連－アルドステロン合成酵素遺伝子型の意義－ (2014)
  • Author(s): 市川麻衣，山本勝司，中屋隆裕，山田実夏，佐藤さつき，今川美智子，牧野耕和，藤井美紀，銭丸康夫，鈴木仁弥，此下忠志，石塚 全，プレム ガチラム，ジャギデジャ ムードレイ
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪、大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] Genetic variation in the renin-angiotensin-aldosterone system and renal survival in Japanese patients with diabetic nephropathy. (2014)
  • Author(s): Makino Y, Konoshita T, Fujii M, Zenimaru Y, Ishizuka T
  • Organizer: 2014 Annual Scientific Meeting of American Society of Hypertension
  • Place of Presentation: New York, USA
  • Year and Date: 2014-05-16 – 2014-05-20
• [Presentation] Measurement of soluble angiotensin-IV receptor (s-AT4), identified through systemic transcriptome analysis of hypertensive and diabetic renal tissue. (2013)
  • Author(s): Konoshita T, Yamada M, Ichikawa M, Sato S, Imagawa M, Makino Y, Fujii M, Wakahara S, Zenimaru Y, Arakawa K, Suzuki J, Kato N
  • Organizer: 23rd European Meeting on Hypertension
  • Place of Presentation: Milan (Italy)
• [Presentation] 網羅的発現遺伝子解析で抽出された高血圧/糖尿病関連因子、アンジオテンシンIV受容体可溶成分（sAT4）の測定 (2013)
  • Author(s): 此下忠志, 山田実夏, 市川麻衣, 木村朋子, 佐藤さつき, 今川美智子, 牧野耕和, 藤井美紀, 銭丸康夫, 若原成行, 稲葉聡, 鈴木仁弥
  • Organizer: 第56回日本腎臓学会学術総会
  • Place of Presentation: 東京、東京国際フォーラム
• [Presentation] 網羅的発現遺伝子解析で抽出された糖尿病関連因子、Insulin regulated aminopeptidase（IRAP/AT4）可溶成分の測定 (2013)
  • Author(s): 此下忠志, 山田実夏, 市川麻衣, 木村朋子, 佐藤さつき, 今川美智子, 牧野耕和, 藤井美紀, 銭丸康夫, 若原成行, 稲葉聡, 鈴木仁弥
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本、熊本市民会館
• [Book] 多発性嚢胞腎診療ガイドライン (2014)
  • Author(s): 日本腎臓学会
  • Total Pages: 69
  • Publisher: 東京医学社