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

Hyperhomocysteinemia is an established risk factor for arterial and venous thrombosis. Recently it has been shown that a C to T mutation at nt positio n 677 in the methylenetetrahydrofolate-reductase (MTHFR) gene is a common c ause of moderately elevated levels of plasma homocysteine in adults. In ord er to investigate whether the newly recognized genetic alteration in the MT HFR gene potentiates the thrombotic tendency in patients with factor V Leid en, we studied 81 unrelated patients with a history of venous thrombosis an d a heterozygous factor V Leiden mutation. In addition, we analyzed 111 fam ily members of 34 families in which the proband had a heterozygous factor V Leiden mutation. In all individuals, factor V Leiden and the MTHFR mutatio n 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 gro up. The prevalence of the homozygous MTHFR mutation was similar in index pa tients (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, a nd 34 years (range 6-72 years) in 71 patients with the factor V Leiden muta tion only. In the family members, the prevalence of thrombosis was not high er in patients with factor V Leiden and +/+ MTHFR genotype than in those wi th only the heterozygous factor V Leiden mutation. We conclude from these d ata that the 677 C to T mutation in the MTHFR gene does not represent a sig nificant additional risk factor for venous thrombosis in patients with fact or V Leiden mutation. (C) 1999 Lippincott Williams & Wilkins.