Unraveling the mystery of homocysteine. A genomic approach.
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KUN Katholieke Universiteit Nijmegen, 2 februari 2005
Promotor : Trijbels, J.M.F. Co-promotores : Blom, H.J., Kluijtmans, L.A.J.
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SubjectUMCN 2.2: Vascular medicine and diabetes; UMCN 5.1: Genetic defects of metabolism
The aims of the present thesis were to explore the molecular genetics and pathophysiology of hyperhomocysteinemia. These objectives will be addressed by the following two research questions: i) Which genetic variants contribute to hyperhomocysteinemia, and ii) What is the pathophysiology of homocysteine in relation to the endothelium-dependent vasodilatation? This thesis is divided into two parts. Part I includes studies in which we investigated whether genetic variation in genes coding for two major regulating enzymes of the homocysteine metabolism (e.g. BHMT and SHMT) is associated with elevated homocysteine levels (chapters 2-3). In part II we have i) investigated the role of endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation, connexins and cytochrome P450 in small renal arterioles of hyperhomocysteinemic rats (chapters 4-6) and, ii) examined the pathophysiology of hyperhomocysteinemia in aorta by microarray analysis (chapters 7-8) and studied the role of a common polymorphism in the eNOS gene in relation to hyperhomocysteinemia (chapter 9).
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