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Study for the gene abnormality encoding depressor hormones in essential hypertension.

Research Project

Project/Area Number 10671044
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNIHON UNIVERSITY

Principal Investigator

SOMA Masayoshi  NIHON UNIVERSITY,MEDICINE,LECTURER, 医学部, 講師 (30246855)

Co-Investigator(Kenkyū-buntansha) WATANABE Yoshiyasu  NIHON UNIVERSITY,MEDICINE,ASSISTANT, 医学部, 助手 (10267049)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Keywordshypertension / gene / polymorphism / receptor / nitric oxide / natriuretic peptide / adenosine / dopamine / ナトリウム利尿ホルモン / レセプター / プロスタサイクリン / 一酸化窒素合成酵素
Research Abstract

(1) Endothelial constitutive NO synthase (ecNOS) gene may be involved in the pathogenesis of essential hypertension (EH). We investigated the possible association between a variable number of tandem repeats (VNTR) polymorphism in intron 4 of the ecNOS gene and EH. The overall distributions of allele frequencies differed significantly between the two groups, with the four-repeat allele more frequent in the EH group than in the normotensive group (p=0.00027, odds ratio=4.0). The four-repeat allele of the ecNOS gene was thus associated with EH and may be a genetic marker of this disease in Japanese subjects.
(2) The natriuretic peptide (NP) family is involved in regulation of blood pressure and fluid volume. We determined the exon/intron organization of human natiuretic peptide receptor the type A (hNPRA) gene. The gene, which spans more than 16 kilobases, is composed of 22 exons, and we isolated the 5'-flanking region of the gene and identified an insertion/deletion mutation in this regio … More n. Our results suggest that this deletion in the hNPRA gene reduces receptor activity and may confer increased susceptibility to developing EH or LVH.
(3) We determined the organization of human natriuretic peptide receptor the type B (NPRB) gene. This gene, which spans approximately 16.5 kilobase (kbp), is composed of 22 exons, and the intron-exon junctions follow the GT-AG rule. Seven hundred fifty basepaires of the 5' flanking region were sequenced using a thermal asymmetric interlaced-PCR (TAIL-PCR) method. This region contains 10 potential Sp1-binding sites and lacks a TATA box. Rapid amplification of cDNA ends (RACE) revealed the transcriptional start site at -14 bp. A CA/GT microsatellite repeat was identified with a hybridization-based method and was converted to sequence tagged site (STS). Association study using a novel GT repeat polymorphism, which associated with EH, was identified. These results suggest that one cause of EH is a mutation in this gene or a closely related gene or region.
(4) The adenosine A2a receptor (A2aAR) gene is thought to be involved in essential hypertension because adenosine elicits vasodilation and decreases arterial blood pressure via this receptor, and because disruption of the A2aAR gene increases blood pressure in mice. Therefore, using a restriction fragment length polymorphism (RFLP) of the A2aAR gene, we performed an association study in patients with EH. Our resullts suggest that the alleles detected by this RFLP polymorphism in the A2aAR gene is not associated with EH.
(5) Defective renal dopamine receptor function have been reported in EH. Using a RFLP of the dopamine D1 redeptor (DRD1) gene, we performed an association study in patients with EH. The alleles detected by this RFLP polymorphism in the DRD1 gene are associated with EH, and they appear to influence diastolic blood pressure of Japanese EH patients. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Mikano Sato. 他: "Dopamine D, receptor gene polymorphism is associated with essential hypertension"Hypertension. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Rehemucluka Duolikm, 他: "An insertion deletion polymorphism in intron 18 of the type B human natriuvetic peptide receptor gene is not associated with cerebral in jarction."Hypertension Research. 23. 173-176 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Nakayama, 他: "Nueleofide sequence of the 5'-flanking region of the thyme A human natriuvetic peptide receptor gene and association analysis using anovel micro* in essential hyper tension"American Journal of Hypertension. 12. 1144-1148 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Rehemudula Duolikun, 他: "Structure of the type B human natriuvetic peptide gene and association of a novel microsatellite polymorphism with essential hypertension"Circulation Research. 84. 605-610 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masayosi Soma, 他: "A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension"American Journal of Hypertension. 11. 1492-1494 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Masayoshi Soma, 他: "NOS gene polymorphism and its influence on card : ovasular disease"Current Opinion in Nephrology and Hypertension. 8. 83-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuki Takahashi, 他: "Organization of the human natriuvetic petiole receptor A gene."Biochemical Biophysical Research Communication. 246. 736-739 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomohiro Nakayama, 他: "Organization of the human prostacyclin synthase gene and association analysis of a novel CA repeat in essential hypertension."Recent Advances in Prostaglandin, Thrmboxane, and Leukotriene. 127-130 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jiro Uwabo, 他: "Association of a variable number of talcum repeats in the encloth linl constitutive nitric oxide syntheses gene with essential hypertension in Japanese"American Journal of Hypertension. 11. 125-128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Uwabo J, Soma M, Nakayama T, Kanmatsuse K: "Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanease."Am J Hypertens. 11. 125-128 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama T, Soma M, Kanmatsuse K: "Oraganization of the human prostacyclin synthase gene and association analysis of a novel CA repeat in essential hypertension."Recent Advances in Prostaglandin, Thromboxane, and Leukotriene Research. 127-130 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takahashi Y, Nakayama T, Soma M, Izumi Y, Kanmatsuse: "Organization of the human natriuretic peptide receptor A gene."Biochem Biophys Res Commun. 246. 736-739 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Soma M, Nakayama T, Satoh M, Uwabo J, Duolikun R, Takahashi Y, Fukuda N, Watanabe Y, Izumi Y and Kanmatsuse K: "A T1083C polymorphism in the human adenosine A2a receptor gene is not associated with essential hypertension."Am J Hypertens. 11. 1492-1494 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Soma M, Nakayama T, Kanmatsuse K: "NOS gene polymorphism and its influence on cardiovascular disease."Cur Opinion in Nephrol Hypertens. 8. 83-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Duolikun R, Nakayama T, Soma M, Takahashi Y, Uwabo J, Sato M, Yoichi I, Kanmatsuse K, Ozawa Y: "Structure of the type B human natriuretic peptide receptor gene and association of a novel microsatellite polymorphism with essential hypertension."Cir Res. 84. 605-610 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama T, Soma M, Takahashi Y, Rehemudula D, Sato M, Uwabo J, Izumi Y, Kanmatsuse K.: "Nucleotide sequence of the 5'-flanking region of the type A human natriuretic peptide receptor gene and association analysis using a novel microsatellite in essential hypertension."Am J Hypertens. 12. 1144-1148 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Rahmutula D, Nakayama T, Soma M, Takahashi Y, Uwabo J, Sato M, Izumi Y, Kanmatsuse K, Ozawa T: "An Insertion/Deletion Polymorphism in Intron 18 of the Type B Human Natriuretic Peptide Receptor Gene Is Not Associated with Cerebral Infarction."Hypertens Res. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sato M, Soma M, Nakayama T, Kanmatsuse K.: "Dopamine D1 Receptor Gene Polymorphism is Associated with Essential Hypertension."Hypertension. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nakayama Tomohiro: "Nucleotide sequence of the S'-Jlanking region of theTypeA human natriuretic peptide receptor gene and association analysis using a novel microsatellete in essential hypertension"American Journal of Hypertension. 12. 1144-1148 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Rehemudula Duolikun: "An Insertion /Deletion polumorphism in infron 18 of the type B human natriuretic peptide receptor gene is not associated with cevebral intarction"Hypertension Research. 23.2(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Duol.Kun Rehemudula: "Structure of the type B human natriuretic peptidie receptor gene and association of a novel microsatellite polymorphism with essential hypertens" Circulation Research, in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Masayoshi Soma: "NOS gene polymerphism and its influence on cardiovascular disease." Current Opinion in Nephrology and Hypertension. 8(1). 83-87 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Masayoshi Soma: "A T1083C polymorphism in the human adenosine A2a receptor gene is not asseciated with essential hypertension." American Journal of Hypertension. 11. 1492-1494 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yukie Takahashi: "Organization of the human natriuretic peptide receptor A gene" Biochemical Biophysical Research Communications. 246. 736-739 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Jiro Uwabu: "Association of a variable number of tandem repeats in the endothelial constitutive nitric oxide synthase gene with essential hypertension in Japanese" American Journal of Hypertension. 11. 125-128 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tomohiro Nakayama: "Organization of the human prostacyclin synthase gene and association analysis of a novel CA repeat in essential Hypertension" Recent Advances in Prostaglandin, Throm bexsine, and Leukotrien Recearch. 127-130 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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