The factor V Leiden mutation which predisposes to thrombosis is not common in patients with antiphospholipid syndrome.
Antiphospholipid syndrome is associated with venous, arterial, and placental thrombosis, possibly through autoantibody impairment of phospholipid-dependent protein C activation. Recently, a missense mutation in the factor V gene (1691 G-->A) has been identified that results in an abnormal factor V product (1). This mutation, known as the Leiden mutation, causes an amino acid substitution of glutamine for arginine at position 506 in the factor V molecule and renders the protein resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized that some individuals with antiphospholipid syndrome may also carry the Leiden mutation, and thus have a "second hit" predisposition to thrombosis. To test this hypothesis, allele-specific hybridization and allele-specific restriction analysis were used to test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of whom had a history of thrombosis. None of the women were heterozygous or homozygous for the factor V mutation. We conclude that the presence of the factor V Leiden mutation is not a prerequisite for the thrombotic events in patients with antiphospholipid syndrome, due to the occurrence of thrombosis seen in patients lacking the factor V mutation.
Dizon-Townson
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D
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, USA.
Hutchison
C
C
Silver
R
R
Branch
D W
DW
Ward
K
K
D000483:Alleles; D016736:Antiphospholipid Syndrome / Q000235:genetics* / Q000503:physiopathology; D001483:Base Sequence; D005165:Factor V / Q000235:genetics*; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D017354:Point Mutation; D013927:Thrombosis / Q000235:genetics* / Q000503:physiopathology
D005165:Factor V