| 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)
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| 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
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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
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