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2002 Fiscal Year Final Research Report Summary

The significance of endothelial nitric oxide synthase gene polymorphisms as genetic markers of hypertensive disorders

Research Project

Project/Area Number 12672236
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

YASUJIMA Minoru  Department of Laboratory Medicine, Hirosaki University School of Medicine, Professor, 医学部, 教授 (90142934)

Co-Investigator(Kenkyū-buntansha) SHOJI Masaru  Department of Laboratory Medicine, Hirosaki University School of Medicine, Associate Professor, 医学部, 助教授 (10226300)
Project Period (FY) 2000 – 2002
Keywordsgene polymorphism / hypertension / restriction enzyme fragment length polymorphism (RFLP) / end-stage renal disease / chronic glomerulonephritis / diabetic nephropathy / angiotensin coverting enzyme I / D polymorphism / Y chromosome Alu insertion polymorphism
Research Abstract

The nitric oxide (NO) plays an important role in the regulation of blood pressure and regional blood flow. Decreased NO activity could contribute to renal vasoconstriction, NaCl retention, and elevated blood pressure. The endothelial NO synthase (ecNOS) gene has been raised as a candidate of genetic risk factor for the development of hypertension and renal diseases. To establish the significance of ecNOS gene polymorphisms as genetic markers of hypertension and its complications, we studied an association between ecNOS gene polymorphisms and hypertension in Japanese subjects. Patients with end-stage renal disease (ESRD) and general regional residents were also enrolled in this study. The genotypes of the ecNOS Glu298Asp and 4b/a variations were determined with PCR based methods including restriction enzyme fragment length polymorphism. In addition, the linkage disequilibrium between 2 ecNOS variations and angiotensin coverting enzyme I/D polymorphism and Y chromosome Alu insertion polymorphism (YAP) was examined. Positive association was found between hypertension and ecNOS Glu298Asp gene polymorphism. However, ecNOS 4b/a gene polymorphism was not associated with hypertension. Systolic blood pressure was significantly lower in the Glu/Glu genotype than in Glu/Asp+Asp/Asp genotypes. Whereas neither Glu298Asp nor 4b/a variations had an association with ESRD including chronic glomerulonephritis and diabetic nephropathy. A significant linkage disequilibrium was found between ecNOS 4b/a gene polymorphism and YAP.
These results suggest that the ecNOS Glu298Asp gene polymorphism may be genetic-susceptibility factors for hypertension.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Kanazawa M, Yasujima M, et al.: "Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist : beyond the rencprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation"Hypertension Research. 25. 447-453 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji M, Yasujima M, et al.: "Lack of association between Y chromosome Alu insertion polymorphism and hypertension"Hypertension Research. 25. 1-3 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kohzuki M, Yasujima M, et al.: "Renal-protective effect of nondepressor dose of cicletanine in diabetic rats with hypertension"Am J Hypertens. 13. 298-306 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami H, Yasujima M, et al.: "Plasma oxysterols and tocopherol in patients with diabetes mellitus and hyperlipidemia"Lipids. 35. 35-38 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato T, Yasujima M, et al.: "Reliable differential diagnosis between osteosarcoma and regenerative bone cells in rats through simultaneous analysis of nuclear DNA content and size"Anal Quant Cytol Histol. 22. 327-332 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato T, Yasujima M, et al.: "Cytofluorometric nuclear DNA content analysis of breast tissues after frozen section diagnosis"Anal Quant Cytol Histol. 22. 70-75 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shoji M, Yasujima M, et al.: "Lack of association of 4G/5G polymorphism in plasminogen activator inhibitor-1 gene with stroke"Advances in Brain Research-Cardiovascular Disorders and Neurodegeneration (edited by Sato K,) (Elsevier Sciences). (In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaru Shojia, Shoji Tsutayab, Chiyako Oshikataa, Minoru Yasujimaa: "Lack of association of 4G/5G polymorphism in plasminogen activator inhibitor-1 gene with stroke"(in press). (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanazawa M, Kohzuki M, Yoshida K, Kurosawa H, Minami N, Saito T, Yasujima M, Abe K: "Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a calcium antagonist: beyond the renoprotective effects of ACE inhibitor monotherapy in a spontaneous hypertensive rat with renal ablation"Hypertens Res. 25. 447-453 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoji M, Tsutaya S, Shimada J, Kojima K, Kasai T, Yasujima M: "Lack of association between Y chromosome Alu insertion polymorphism and hypertension"Hypertens Res. 25. 1-3 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shoji M, Tsutaya S, Saito R, Takamatu H, Yasujima M: "Positive association of endothelial nitric oxide synthase gene polymorphism with hypertension in northern Japan"Life Sci. 66. 2557-2562 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kohzuki M, Wu XM, Kamimoto M, Yoshida K, Nagasaka M, Kanazawa M, Yasujima M, Saito T, Sato T: "Renal-protective effect of non-depressor dose of cicletanine in diabetic rats with hypertension"Am J Hypertension. 13. 198-306 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami H, Tamazawa N, Matsui J, Yasujima M, Suda T: "Plasma oxysterols and tocopherol in patients with diabetes mellitus and hyperlipidemia"Lipids. 35. 333-338 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato T, Miura T, Nakano K, Nozaka H, Sato T, Ishikawa T, Chiba M, Kanagawa Y, Kizawa C, Hasegawa S, Yasujima M: "Reliable differential diagnosis between osteosarcoma and regenerative bone cells in rats through simultaneous analysis of nuclear DNA content and size"Anal Quant Cytol Histol. 22. 327-332 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato T, Chiba M, Kamiyama T, Miura T, Kanagawa Y, Nakano K, Sato T, Ishikawa T, Nozaka H, Kogawa R, Yasujima M: "Cytofluorometric nuclear DNA content analysis of breast tissues after frozen section diagnosis"Anal Quant Cytol Histol. 22. 70-75 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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