Increased risk for venous thrombosis in carriers of the prothrombin G-->A20210 gene variant.
BACKGROUND
A mutation in the prothrombin gene (G-->A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis.


OBJECTIVE
To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis.


METHODS
Case-control study.


METHODS
Two thrombosis centers in southern Italy.


METHODS
281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls.


METHODS
Medical history was collected on standardized questionnaires. The presence of prothrombin G-->A2020 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function.


RESULTS
In 150 controls, increased prothrombin activity (P < 0.001) was associated with the prothrombin A20210 allele. This allele was more frequent in patients than in controls (8.01% compared with 2.29%; P < 0.001) and was associated with an increased risk for thrombosis (odds ratio, 3.88 [95% CI, 2.23 to 6.74]). The increased prevalence of this allele was independent of the presence of the factor V Leiden mutation. After adjustment for sex, age, arterial thrombosis, and factor V Leiden mutation, the risk was still significantly elevated (odds ratio, 3.13 [CI, 1.89 to 5.21]). Moreover, the overall prevalence of inherited coagulation abnormalities was significantly higher in patients with thrombosis of the lower extremities than in patients with thrombosis of the upper extremities (odds ratio, 3.77 [CI, 1.10 to 12.93]). Fourteen patients carried both the prothrombin G-->A20210 and factor V Leiden mutations.


CONCLUSIONS
The prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis, particularly in patients with a history of thrombosis of the lower extremities.
Margaglione
M
M
IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Brancaccio
V
V
Giuliani
N
N
D'Andrea
G
G
Cappucci
G
G
Iannaccone
L
L
Vecchione
G
G
Grandone
E
E
Di Minno
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017354:Point Mutation; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013223:Statistics as Topic; D011795:Surveys and Questionnaires; D013924:Thrombophlebitis / Q000097:blood / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin