Methylenetetrahydrofolate reductase (MTHFR) deficiency is a common inborn error of folate metabolism. The phenotypic spectrum ranges from severe neurologic deterioration and early death to asymptomatic adults. In the classic form, both thermostable and thermolabile enzyme variants have been identified 1. The 677C-T mutation in the MTHFR gene results in an alanin 222-to-valin (A222V) substitution. Individuals homozygous for the mutation have significantly elevated plasma homocysteine levels. Thus, the 677C-T mutation may represent an important genetic risk factor in vascular disease2. Studies of the 677C-T mutation in cardiovascular patients and controls show that homozygosity for this frequent mutation in the MTHFR gene is associated with a 3-fold increase in risk for premature cardiovascular disease3. Both hyperhomocysteinemia due to the 677C-T mutation and factor V Leiden are risk factors for recurrent venous thrombosis. It was found that the risk of thrombosis appeared higher for individuals who had both risk factors4.

This kit uses hybridization probes to detect variations running a melting curve. The melting-curve peaks discriminate between the “wild-type”, the variant 677T and the heterozygous genotype.

1 Rosenblatt, D. S.; Lue-Shing, H.; Arzoumanian, A.; Low-Nang, L.; Matiaszuk, N. : Methylenetetrahydrofolate reductase (MR) deficiency: thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts. Biochem. Med. Metab. Biol. 47: 221-225, 1992

2 A. J.; van den Heuvel, L. P.; Rozen, R. : A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet. 10: 111-113, 1995.

3 Kluijtmans, L. A. J.; van den Heuvel, L. P. W. J.; Boers, G. H. J.; Frosst, P.; Stevens, E. M. B.; van Oost, B. A.; den Heijer, M.; 3) Trijbels, F. J. M.; Rozen, R.; Blom, H. J. : Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am. J. Hum. Genet. 58: 35-41, 1996

4 Keijzer, M. B. A. J.; den Heijer, M.; Blom, H. J.; Bos, G. M. J.; Willems, H. P. J.; Gerrits, W. B. J.; Rosendaal, F. R. : Interaction between hyperhomocysteinemia, mutated methylenetetrahydrofolatereductase (MTHFR) and inherited thrombophilic factors in recurrent venous thrombosis. Thromb. Hemost. 88: 723-728, 2002

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