Plasma homocyst(e)ine levels, 677C to T mutation in the methylenetetrahydrofolate reductase gene, and factor V Leiden mutation in patients with ischemic cerebrovascular disease

Mild to moderate elevation of plasma homocyst(e)ine is an established risk factor of atherosclerosis and its complications, including stroke. Recently, a 677C to T mutation in the gene of the 5,10-Methylenetetrahydrofolate reductase (MTHFR) has been described which might represent a common hereditary cause of hyperhomocyst(e)inemia. Deficiencies of folate and vitamin-B12 belong to the most common acquired causes of hyperhomocyst(e)inemia. Previous studies suggest a relationship between the 677C to T MTHFR mutation status, folate level, and homocyst(e)ine level. However, only very few data exist about the possible role of the 677C to T MTHFR mutation in patients with ischemic cerebrovascular disease, particularly in relation to other known vascular risk factors. Another recently described mutation, the factor V Leiden mutation, which renders factor V resistant to inactivation, is the most common hereditary risk factor of venous thrombosis. The role of the factor V Leiden mutation for arterial vascular events has not been completely determined. Experimental studies suggest a pathophysiological link between homocyst(e)ine and factor V activity. Possible clinical consequences of the combined occurrence of these two mutations in patients with cerebrovascular disease have not been investigated. In the present study, 120 patients who suffered an ischemic cerebrovascular event (TIA/stroke) and 120 age- and sex- matched control subjects are to be investigated with respect to plasma homocyst(e)ine levels as well as folate and vitamin-B12 levels. Furthermore, the 677C to T MTHFR mutation status and the factor V Leiden mutation status will be determined. Following questions are to be answered: (1) The prevalence of the 677C to T mutation and of the factor V Leiden mutation in patients with ischemic cerebrovascular disease and in an age- and sex-matched control population. (2) The relation between the MTHFR mutation status (homozygous carrier/heterozygous carrier/no mutation) and homocyst(e)ine-levels in patients with cerebrovascular disease and in age- and sex- matched control subjects under consideration of folate status, vitamin-B12 status and established vascular risk factors. (3) Possible clinical consequences of the combined occurrence of the 677C to T mutation and/or elevated homocyst(e)ine levels and the factor V Leiden mutation in patients with ischemic cerebrovascular disease.