THE METHYLENETETRAHYDROFOLATE REDUCTASE TT677 GENOTYPE IS ASSOCIATED WITH VENOUS THROMBOSIS INDEPENDENTLY OF THE COEXISTENCE OF THE FV LEIDEN AND THE PROTHROMBIN A(20210) MUTATION

A polymorphism, C --> T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteine mia, a risk factor for venous thrombosis. We have investigated the fre quency of the TT genotype in 277 consecutive patients with confirmed d eep venous thrombosis and 431 healthy subjects. The TT MTHFR genotype was more frequent in patients than in controls (25.6% vs. 18.1%; p = 0 .016). The risk of thrombosis among carriers of this genotype was sign ificantly increased [odds ratio: 1.6 (95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotype was 2.0 (95% CI: 1.3-3.1) in sub jects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factor s for venous thrombosis. Factor V Leiden and prothrombin G-->A(20210) are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A(20210) mutations, a significant associati on was also observed. After adjustment for sex: FV Leiden and prothrom bin A(20210) mutation, the estimated risk of venous thrombosis among c arriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTH FR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.