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2001 Fiscal Year Final Research Report Summary

ESTABLISHMENT OF DNA TESTING SYSTEMS FOR THE DIAGNOSES OF GENETIC SUSCEPTIBILITY OF ATHEROSCLEROSIS AND THROMBOSIS

Research Project

Project/Area Number 11557206
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory medicine
Research InstitutionKeio University

Principal Investigator

WATANABE Kiyoaki  School of Medicine, Keio University, Professor, 医学部, 教授 (20101983)

Co-Investigator(Kenkyū-buntansha) TAKEI Izumi  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (80129519)
TANAHASHI Norio  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (10124950)
MURATA Mitsuru  School of Medicine, Keio University, Assistant Professor, 医学部, 講師 (50174305)
IWANAGA Shiro  School of Medicine, Keio University, Assistant Professor, 医学部, 助手 (70213303)
Project Period (FY) 1999 – 2001
KeywordsATHEROSCLEROSIS / THROMBOSIS / GENETICS / POLYMORPHISM / GENETIC TESTING / RISK FEACTORS
Research Abstract

Genetic factors in combination with a number of environmental risk factors are involved in a predisposition to atherosclerosis and thrombosis. Coronary artery disease (CAD) and ischemic cerebrovascular disease (CVD) are typical human attributes that have a complex multifactorial etiology. The aim of the present study was to clarify the relationship between genetic polymorphisms found in factors relevant to thrombosis and disease phenotypes (i.e., sites of thrombus and severity of atherosclerosis), through a series of case-control studies involving patients with CAD, CVD, and deep vein thrombosis. We also aimed to establish systems to comprehensively evaluate the contribution of genetic factors to the pathogenesis of thrombosis in the Japanese populations, where allele frequencies are known to be quite different than Caucasians.
Polymorphisms in platelet GPIba receptor and coagulation factor XII were involved in susceptibility to CVD. We also found that polymorphisms in CETP and MTHFR we … More re associated with macroangiopathy in type 2 diabetes. In addition, factor XII polymorphism was associated with calcification of abdominal aorta in diabetic patients. Another novel finding of this study was the relationships between the activities or concentrations of certain factors (paraoxonase, homocystein, activated coagulation factor XII, ANP) and polymorphisms within each gene.
As previously shown in acquired factors, combinations of multiple genetic factors are believed to be crucial for the development of thrombotic disorders. We thus developed a new strategy to simultaneously analyze the genotypes of relevant polymorphisms. We also established methods to amplify relevant DNA fragments from whole blood in PCRs.
The ultimate goal of the clinical appreciation of polymorphic markers is to identify subgroups of individuals who are best prevented from developing diseases, or who respond best to dietary, behavioral, or pharmacologic interventions. For this purpose, polymorphisms need to be investigated not only in relation to disease susceptibility, but also with regard to responsiveness to treatment, and gene-environment interactions. Also, development of novel strategies to comprehensively assess the risk factors particular to the Japanese is warranted. Less

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Oguchi S, Ito D, Murata M, Yashida T, et al.: "Genoiyps distnbutaon of the 46C/T polymorphism of coagulatiou factor XII in the Japanese population : absence of its association with ischcmic cerebrovascuiar disease"Thromb Haemast. 83. 178-179 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsubara Y, Hayakawa T, Tsuda T, Takeshita E, et al.: "Angiotensin convening enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasmanogen activator inhibitor-1 in healtby Japanese population"Blood Coagulation and Fibrinolysis. 11. 115-120 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sonoda A, Murata M, Ito D, Ohta A, et al.: "Association between platelet glycoprotein Ib α genotype and ischemic ccrebrovascular disease"Stroke. 31. 493-497 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishil K, Oguchi S, Murata M, Mitsuyoshi Y, et al.: "Activated factor XII levels are depedent on factor XII 46C/T genotypes an factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects"Blood Coagulation and Fibrinolysis 11:115-120,2000. 11. 277-284 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito D, Murata M, Watanabe K, Yashida T: "C242T polymorphism of NADPH oxidase p22 phox gene and ischemic cerebrovascular disease"Stroke. 31. 936-939 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Meguro S, Takei I, Murata M, Hirose H: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Atheroscierosis. 156. 151-156 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Oguchi S., Ito D., Murata M., Yoshida T., et al.: "Genotype distribution of the 46C/T polymorphism of coagulation factor XII in the Japanese population: absence of its association with ischemic cerebrovascular disease"Thromb Haemost. 83. 178-179 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsubara Y., Hayakawa T., Tsuda T., Takeshita E., et al.: "Angiotensin converting enzyme insertion/deletion polymorphism is associated with plasma antigen levels of plasminogen activator inhibitor-1 in healthy Japanese population"Blood Coagulation and Fibrinolysis. 11. 115-120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sonoda A., Murata M., Ito D., Ohta A., et al.: "Association between platelet glycoprotein Ib α genotype and ischemic cerebrovascular disease"Stroke. 31. 493-497 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishii K., Oguchi S., Murata M., Mitsuyoshi Y., et al.: "Activated factor XII levels are dependent on factor XII 46C/T genotypes and factor XII zymogen levels, and are associated with vascular risk factors in patients and healthy subjects"Blood Coagulation and Fibrinolysis. 11. 277-284 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito D., Murata M., Watanabe K., Yoshida T. et al.: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Stroke. 31. 936-939 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Meguro S., Takei I., Murata M., Hirose H., et al.: "Cholesteryl ester tranffer protein polymorphism is associated with macroangiopathy in Japanese type 2 diabetes mellitus"Atherosclerosis. 151. 151-156 (2001)

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

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Published: 2003-09-17  

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