Impact of the factor II: G20210A variant on the risk of venous thromboembolism in relatives from families with the factor V: R506Q mutation.
OBJECTIVE
Factor V: R506Q mutation and the prothrombin G20210A variant (factor II: G20210A variant) are associated with an increased risk of venous thromboembolism (VTE). In cohorts of unrelated patients a cosegregation of both mutations has been shown to be associated with an increased risk of developing VTE. The aim of this study was to investigate the impact of the coinheritance of both mutations on the risk of VTE in relatives of symptomatic carriers of the factor V: R506Q mutation and the factor II: G20210A variant.


METHODS
Four families with 48 family members were investigated for the presence of the factor V: R506Q mutation and the factor II: G20210A mutation, and their clinical history was evaluated.


RESULTS
VTE was more frequent in family members with a combined defect (3/10; 30%) compared to those with a single mutation (1/16; 6%) or without a defect (1/12; 8%). The probability for VTE for 40-yr-old individuals with both mutations, a single mutation and no mutation was 56%, 12% and 20%, respectively.


CONCLUSIONS
These data suggest that the G to A transition at position 20210 of the prothrombin gene leads to an increase in the risk of VTE in carriers of the factor V: R506Q mutation. The determination of the factor II: G20210A variant in index patients carrying a factor V: R506Q mutation and, if present, in family members may help to identify individuals who are at high risk for VTE.
Rintelen
C
C
University of Vienna Medical School, First Department of Medicine, Division of Hematology and Blood Coagulation, Vienna, Austria. claudia.rintelen@akh-wien.ac.at
Pabinger
I
I
Bettelheim
P
P
Lechner
K
K
Kyrle
P A
PA
Knöbl
P
P
Schneider
B
B
Mannhalter
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011516:Prothrombin / Q000235:genetics*; D012306:Risk; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics*
D005165:Factor V; D011516:Prothrombin