Genetic susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations.
OBJECTIVE
This study's objective was to evaluate the association between venous thromboembolism during pregnancy and the postpartum period and the factor V Arg 506 Gln (factor V Leiden), the prothrombin G20210A, and methylenetetrahydrofolate reductase C677T polymorphisms.


METHODS
In this case-control study 42 case patients and 213 control subjects (parous age-matched women without history of thrombosis) were genotyped for all the polymorphisms. Moreover, antiphospholipid antibodies and protein C, protein S, and antithrombin III deficiencies were investigated in each case.


RESULTS
Ten case patients (23.8%) and 4 control subjects (1.9%; odds ratio 16.3, 95% confidence interval 4.8-54.9) carried the factor V Leiden mutation; 13 case patients (31.0%) and 9 control subjects (4.2%; odds ratio 10.2, 95% confidence interval 4.0-25.9) were carriers of the prothrombin G20210A allele. Finally, 12 case patients (28.6%) and 34 control subjects (16.0%; odds ratio 2.1, 95% confidence interval 1.0-4.5) were homozygotes for methylenetetrahydrofolate reductase C677T. Overall, mutations were found in 25 case patients (59.5%) and 47 control patients (22.2%; odds ratio 5.2, 95% confidence interval 4.9-19.6). One patient carried the antithrombin III deficiency and 1 the protein S deficiency, whereas 2 women had a primary antiphospholipid syndrome.


CONCLUSIONS
The significant risk estimates of having a pregnancy-related venous thromboembolism in the presence of the prothrombotic genetic risk factors analyzed suggest to screen for these mutations women with a personal history of thromboembolic events during pregnancy or the postpartum period.
Grandone
E
E
Unità di Aterosclerosi e Trombosi, Casa Sollievo della Sofferenza, S. Giovanni Rotondo, Divisione di Ematologia, Naples, Italy.
Margaglione
M
M
Colaizzo
D
D
D'Andrea
G
G
Cappucci
G
G
Brancaccio
V
V
Di Minno
G
G
D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation / Q000502:physiology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011516:Prothrombin / Q000235:genetics; D011655:Pulmonary Embolism / Q000235:genetics; D013923:Thromboembolism / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)