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Articles

Title: Hyperhomocysteinemia - an important risk factor for ischemic heart disease

Author:
Krzysztof Chiżyński
Type:
Editorial article
Language:
PL
Journal:
Polish Journal of Cardiology
Year:
2002
Volume:
4
Number:
2
Start page:
103
Final page:
108
ISSN:
1507-5540
Keywords:
hyperhomocysteinemia, ischaemic heart disease, C677T MTHFR polymorphism
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Hyperhomocysteinemia is increasingly recognised as an independent risk factor for coronary artery disease. Homocysteine-induced atherosclerosis is characterised by endothelial dysfunction and injury followed by platelet activation and thrombus formation. In blood, homocysteine is oxidised to form homocysteine, mixed disulphides, and homocysteine thiolactone. Homocysteine is metabolised by either remethylation or transsulfuration. In the remethylation cycle, homocysteine is salvaged by he acquisition of a methyl group in a reaction catalysed by methionine synthase. Increases in homocysteine plasma levelsare caused by nu-tritional deficiencies in vitamin cofactors, or by genetic defects in the enzymes which are involved in the me-tabolism of this amino acid. Genetic defect, a thermolabile variant of MTHFR has been described which is caused by a point mutation (C677T) in the coding region for the MTHFR binding site, leading to the substi-tution of valine for alaninę. It has been shown that this gene variation was associated with increased levels of homocysteine. In many studies, the potential link between this gene polymorphism and ischaemic heart disease has been investigated and some investigators identified the TT genotype as a risk factor of cardio-vascular disease. Vitamin B12 is an essential cofactorfor methionine synthase, N5-methyl-tetrahydrofolate is the methyl donor in this reaction, and N5, N10-methylenetetrahydrofolate reductase (MTHFR) functions as a catalyst in the remethylation process. Cystathionine |3-synthase deficiency is the most common gene-tic cause of severe hyperhomocysteinemia. Other factors beyond genetic variation are also associated with increased levels of homocysteine. Increased homocysteine plasma levels are caused by nutritional deficien-cies in vitamin cofactors: folie acid and(or) vitamin B6and B12, medical therapy (the use folie acid antagoni-stse.g. methotrexate, vitamin B6or B12antagonists, phenytoin, hormonal therapy), endocrine disturbances, renal insufficiency, smoking, alcohol intake. In generał population there are 5-10% patients with hyperhomocysteinemia. In patients with angiographically diagnosed coronary stenosis hyperhomocysteinemia is re-cognized as a risk factor for sudden cardiac death.