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Contains fulltext : 30131_molegeano.pdf (Publisher’s version ) (Open Access) Homocysteine is a intermediary product of protein metabolism. A high concentration of homocysteine in the blood is associated with a higher risk of cardiovascular disease, including venous thrombosis. Homocysteine levels are in part determined by genetic factors and vitamin intake (such as vitamin B12). The main goal of the presented research was to identify genetic factors (polymorphisms) that affect homocysteine levels and to assess if these polymorphisms also increased the risk of recurrent venous thrombosis. In addition, we evaluated vitamin B12 as a risk factor of recurrent venous thrombosis. We investigated a polymorphism in the catechol-O-methyltransferase gene, which is involved in so-called 'transmethylation reactions', in relation to homocysteine levels. Individuals carrying this polymorphism had higher homocysteine levels than subjects that did not carry this variant. In addition, this polymorphism was more common in recurrent venous thrombosis cases than the general population. This supports the hypothesis that high homocysteine reflects a disturbed transmethylation, which increases venous thrombosis risk. We also developed a method to study metabolites in the blood that report on the ability of our body to perform transmethylation reactions. It appeared that the way the blood samples were stabilized was of great importance for the reliability of our method. Future studies will have to point out whether a disturbed transmethylation is involved in the aetiology of venous thrombosis. Finally, we show that a low vitamin B12 status, which is a cause of high homocysteine levels, is associated with an increased risk of recurrent venous thrombosis. Measuring methylmalonic acid, a marker of intracellular vitamin B12 availability, seems more suitable for measuring vitamin B12 status than plasma vitamin B12 itself. RU Radboud Universiteit Nijmegen, 11 januari 2007 Promotor : Hermus, A.R.M.M. Co-promotores : Heijer, M. den, Blom, H.J. 165 p.

Homocysteine is a risk factor for venous thrombosis. Elevated concentrations can be treated with folic acid, vitamin B6 and vitamin B12. The main study (chapter 9) in this thesis is a randomized placebo-controlled trial in which patients with a first event of deep-vein thrombosis or pulmonary embolism are treated with above mentioned vitamins or a placebo. There was no effect of vitamin treatment on recurrent thrombosis. A case-control study is described whichs shows that elevated homocysteine concentrations are a risk factor for venous thrombosis and pulmonary embolism in elderly patients (chapter 7). Two studies deal with acidic citrate as an anticoagulant in blood collection tubes. We show that acidic citrate stabilizes homocysteine concentrations at room temperature (chapter 3) and that the homocysteine concentrations measured in blood collection tubes with acidic citrate as anticoagulant correlate well with the concentrations measured in blood tubes with EDTA as anticoagulant (chapter 4). One study compared patients on and off anticoagulant therapy. There was no influence of coumarin derivatives on plasma homocysteine concentrations (chapter 5). The endogeous thrombin potential is not different in patients with high homocysteine concentrations in comparison to patients with low homocysteine concentrations (chapter 6).

Contains fulltext : 49066.pdf (Publisher’s version ) (Open Access) KUN Katholieke Universiteit Nijmegen, 04 februari 2005 Promotor : Schalkwijk, J. Co-promotor : Heijer, M. den 144 p.