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Molecular analysis of heterogeneity in human platelet aggregation response

Research Project

Project/Area Number 17590482
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionHirosaki University

Principal Investigator

SHOJI Masaru  Hirosaki University, School of Medicine, Associate Professor, 医学部, 助教授 (10226300)

Co-Investigator(Kenkyū-buntansha) YASUJIMA Minoru  Hirosaki University, School of Medicine, Professor, 医学部, 教授 (90142934)
SUGIMOTO Kazuhiro  Hirosaki University, University Hospital, Lecturer, 医学部附属病院, 講師 (70271799)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsgene expression / microRNA / vasopressin / peripheral CD34(+) stem cell / microarray / mass spectrometry / 遺伝子 / シグナル伝達 / 生体分子 / バゾプレシンV1a受容体
Research Abstract

There is a significant inter-individual divergence in the platelet aggregation response to arginine vasopressin (AVP). In the present study, high-throughput microarray analysis was conducted to explore molecules, which are responsible for the heterogeneity. Responders and non-responders were divided using platelet aggregation analyzer MCM hematracer 313 (Model PAM-12C). Hitachi Ace-Gene micro array analysis showed characteristic gene expression profiling. Namely, responder platelets had increased gene expressions of sodium channel, voltage-gated, type., alpha, mannose-P-dolichol utilization defect 1、eukaryotic translation termination factor 1、cysteine and glycine-rich protein 2、and general transcription factor IIH, polypeptide 2,44kDa. In non-responder platelets, genes including component of oligomeric golgi complex 6、Hermansky-Pudlak syndrome 3、PERM domain containing 1、adenosine monophosphate deaminase 2 (isoform L) nudix-type motif 1、and cell growth regulator with ring finger domain 1 were upregulated. Mass spectrometry analysis demonstrated increased platelet protein levels of protease serine 4 isoform B、and keratin 1b、trypsin family in responders and of TPMsk1、TPM3 protein、and YWHAZ protein in non-responders. There were also increased microRNA levels including hsa let 7d、hsa let 7e、hsa miR 198、hsa miR 99b、and hsa miR 98 in AVP stimulated peripheral CD34(+) stem cells (megakaryocyte progenitor cells). AVP Vla receptor gene polymorphism 242C/T showed an association with its gene expression. From these results, numbers of factors were likely to be responsible for the inter-individual heterogeneity in the platelet aggregation response to AVP.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 2005 Other

All Journal Article (22 results) Book (1 results)

  • [Journal Article] Association of novel promoter single nucleotide polymorphisms in vaso-pressin Vla receptor gene with essential hypertension in nonphese Jananese2007

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      Journal of Human Hypertension (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of vasopressin Vla receptor in hypertension, diabetes mellitus and platelet functions genetic polymorphism study2007

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      Hirosaki Med J 58

      Pages: 35-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Role of vasopressin Vla receptor in hypertension, diabetes mellitus and platelet functions : genetic polymorphism study.2007

    • Author(s)
      Hasan KN, Shoji M, Sugimoto K, Tsutaya S, Yasujima M.
    • Journal Title

      Hirosaki Med J 58

      Pages: 35-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of novel promoter single nucleotide polymorphisms in vasopressin Vla receptor' gene with essential hypertension in nonobese Japanese2007

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      Journal of Human Hypertension (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hynokalemic periodic paralysis2006

    • Author(s)
      Kageyama K, et al.
    • Journal Title

      J Endocrinol Invest 29

      Pages: 928-933

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Study of Via vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness2006

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      J Clin Lab Anal 20

      Pages: 87-92

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel mutation of the thiazide-sensitive sodium chloride co-transporter gene in a Japanese family with Gitelman syndrome.2006

    • Author(s)
      Terui K, et al.
    • Journal Title

      Clin Nephrol 65

      Pages: 57-60

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis.2006

    • Author(s)
      Kageyama K, Terui K, Tsutaya S, Matsuda E, Shoji M, Sakihara S, Nigawara T, Takayasu S, Moriyama T, Yasujima M, Suda T.
    • Journal Title

      J Endocrinol Invest 29

      Pages: 928-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel mutation of the thiazide-sensitive sodium chloride cotransporter gene in a Japanese family with Gitelman syndrome.2006

    • Author(s)
      Terui K, Shoji M, Yamashiki J, Hirai Y, Ishiguro A, Tsutaya S, Kageyama K, Yasujima M, Suda T.
    • Journal Title

      Clin Nephrol 65

      Pages: 57-60

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Study of Vla vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.2006

    • Author(s)
      Hasan KN, Shoji M, Tsutaya S, Kudo R., Matsuda E, Saito J, Kimura T, Yasujima M.
    • Journal Title

      J Clin Lab Anal 20

      Pages: 87-92

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Study of Vla vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.2006

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      J Clin Lab Anal 20

      Pages: 87-92

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis.2006

    • Author(s)
      Kageyama K, et al.
    • Journal Title

      J Endocrinol Invest 29

      Pages: 928-933

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 高血圧-最新の研究動向- : 血管内皮型NO合成酵素遺伝子2006

    • Author(s)
      庄司 優, 保嶋 実
    • Journal Title

      日本臨床 64・増5

      Pages: 411-415

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 高血圧-最新の研究動向- : BNP2006

    • Author(s)
      庄司 優, 保嶋 実
    • Journal Title

      日本臨床 64・増6

      Pages: 133-136

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Study of V1a vasopressin receptor gene single nucleotide polymorphisms in platelet vasopressin responsiveness.2006

    • Author(s)
      Hasan KN, et al.
    • Journal Title

      J Clin Lab Anal (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Diagnosis of a case of Gitelman's syndrome based on renal clearance studies and gene analysis of a novel mutation of the thiazide-sensitive Na-Cl cotransporter2005

    • Author(s)
      Kageyama K, et al.
    • Journal Title

      J Endocrinol Invest 28

      Pages: 822-826

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diagnosis of a case of Gitelman's syndrome based on renal clearance studies and gene analysis of a novel mutation of the thiazide-sensitive Na-Cl cotransporter.2005

    • Author(s)
      Kageyama K, Terui K, Shoji M, Tsutaya S, Matsuda E, Sakihara S, Nigawara T, Moriyama T, Yasujima M, Suda T.
    • Journal Title

      J Endocrinol Invest 28

      Pages: 822-626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Diagnosis of a case of Gitelman's syndrome based on renal clearance studies and2005

    • Author(s)
      Kageyama K, et al.
    • Journal Title

      J Endocrinol Invest 28

      Pages: 822-826

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ACTH2005

    • Author(s)
      庄司 優, 須田俊宏
    • Journal Title

      medicina 42

      Pages: 320-321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] バソプレシン2005

    • Author(s)
      庄司 優, 須田俊宏
    • Journal Title

      medicina 42

      Pages: 322-323

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 疾患群の遺伝学的検査と遺伝子検査:腎・血管疾患2005

    • Author(s)
      庄司 優, 保嶋 実
    • Journal Title

      日本臨床 63・増12

      Pages: 223-227

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of novel promoter single nucleotide polymorphisms in vasopressin Vla receptor gene with essential hypertension in nonobese Japanese.

    • Author(s)
      Hasan KN, Shoji M, Sugimoto K, Tsutaya S, Matsuda E, Kudo R, Nakaji S, Suda T, Yasujima M.
    • Journal Title

      J Human Hypertension (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] 下垂体後葉系.臨床内分泌・代謝学、(須田俊宏編)2007

    • Author(s)
      庄司優
    • Total Pages
      351
    • Publisher
      弘前大学出版会
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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