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
C. Rintelen et al., 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, BL COAG FIB, 10(2), 1999, pp. 101-105
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.