The Methylenetetrahydrofolate Reductase TT677 Genotype Is Associated with Venous Thrombosis Independently of the Coexistence of the FV Leiden and the Prothrombin A 20210 Mutation
Maurizio Margaglione, Giovanna D’Andrea, Marina d’Addedda, Nicola Giuliani, Giuseppe Cappucci, Luigi Iannaccone, Gennaro Vecchione, Elvira Grandone, Vincenzo Brancaccio, Giovanni Di Minno
From Unità di Aterosclerosi e Trombosi, I.R.C.C.S. “Casa Sollievo della Sofferenza”, S. Giovanni Rotondo, Divisione di Ematologia, Unità di Coagulazione, Ospedale “A. Cardarelli”, Napoli, and Istituto di Medicina Interna e Geriatria, Università di Paler
Summary A polymorphism, CRT677, in the methylenetetrahydrofolatereductase (MTHFR) gene has been identified as a cause of mildhyperhomocysteinemia, a risk factor for venous thrombosis. We haveinvestigated the frequency of the TT genotype in 277 consecutivepatients with confirmed deep venous thrombosis and 431 healthysubjects. The TT MTHFR genotype was more frequent in patients thanin controls (25.6% vs. 18.1%; p = 0.016). The risk of thrombosis amongcarriers of this genotype was significantly increased [odds ratio: 1.6(95% CI: 1.1-2.3)]. The estimated risk associated with the TT genotypewas 2.0 (95% CI: 1.3-3.1) in subjects with (n = 122), and 1.3 (95% CI:0.8-2.0) in those without (n = 155) predisposing (hereditary, acquiredor circumstantial) risk factors for venous thrombosis. Factor V Leidenand prothrombin GRA 20210 are known risk factors for venous thrombosis.After stratification for FV Leiden and prothrombin A 20210 mutations,a significant association was also observed. After adjustmentfor sex, FV Leiden and prothrombin A 20210 mutation, the estimated riskof venous thrombosis among carriers of the TT MTHFR genotype was1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independentlyassociated with venous thrombosis, mainly among individuals with ahigh risk profile.