No evidence for an increased risk of venous thrombosis in patients with factor V Leiden by the homozygous 677 C to T mutation in the methylenetetrahydrofolate-reductase gene.

Abstract

Hyperhomocysteinemia is an established risk factor for arterial and venous thrombosis. Recently, it has been shown that a C to T mutation at nt position 677 in the methylenetetrahydrofolate-reductase (MTHFR) gene is a common cause of moderately elevated levels of plasma homocysteine in adults. In order to investigate whether the newly recognized genetic alteration in the MTHFR gene potentiates the thrombotic tendency in patients with factor V Leiden, we studied 81 unrelated patients with a history of venous thrombosis and a heterozygous factor V Leiden mutation. In addition, we analyzed 111 family members of 34 families in which the proband had a heterozygous factor V Leiden mutation. In all individuals, factor V Leiden and the MTHFR mutation were tested and the occurrence of venous thrombotic events was evaluated retrospectively. Seventy-seven healthy subjects without the factor V Leiden mutation or any other known thrombotic risk factor served as a control group. The prevalence of the homozygous MTHFR mutation was similar in index patients (10 of 81, 12%) and in the control group (10 of 77, 13%). The median age at first thrombosis in index patients was 32 years (range 22-69 years) in 10 patients with heterozygous factor V Leiden and T/T MTHFR mutation, and 34 years (range 6-72 years) in 71 patients with the factor V Leiden mutation only. In the family members, the prevalence of thrombosis was not higher in patients with factor V Leiden and +/+ MTHFR genotype than in those with only the heterozygous factor V Leiden mutation. We conclude from these data that the 677 C to T mutation in the MTHFR gene does not represent a significant additional risk factor for venous thrombosis in patients with factor V Leiden mutation.