The Methylenetetrahydrofolate Reductase TT677 Genotype Is Associated with Venous Thrombosis Independently of the Coexistence of the FV Leiden and the Prothrombin

Maurizio Margaglione; Giovanna D’Andrea; Marina d’Addedda; Nicola Giuliani; Giuseppe Cappucci; Luigi Iannaccone; Gennaro Vecchione; Elvira Grandone; Vincenzo Brancaccio; Giovanni Di Minno

doi:10.1055/s-0037-1615091

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 79(05): 907-911
DOI: 10.1055/s-0037-1615091

Review Article

Schattauer GmbH

The Methylenetetrahydrofolate Reductase TT677 Genotype Is Associated with Venous Thrombosis Independently of the Coexistence of the FV Leiden and the Prothrombin

A²⁰²¹⁰ Mutation

Maurizio Margaglione

¹From 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 Palermo, Italy

,

Giovanna D’Andrea

¹From 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 Palermo, Italy

,

Marina d’Addedda

¹From 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 Palermo, Italy

,

Nicola Giuliani

¹From 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 Palermo, Italy

,

Giuseppe Cappucci

¹From 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 Palermo, Italy

,

Luigi Iannaccone

¹From 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 Palermo, Italy

,

Gennaro Vecchione

¹From 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 Palermo, Italy

,

Elvira Grandone

¹From 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 Palermo, Italy

,

Vincenzo Brancaccio

¹From 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 Palermo, Italy

,

Giovanni Di Minno

¹From 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 Palermo, Italy

› Author Affiliations

Abstract

Summary

A polymorphism, C→T677, in the methylenetetrahydrofolate reductase (MTHFR) gene has been identified as a cause of mild hyperhomocysteinemia, a risk factor for venous thrombosis. We have investigated the frequency of the TT genotype in 277 consecutive patients with confirmed deep 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 significantly 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 subjects with (n = 122), and 1.3 (95% CI: 0.8-2.0) in those without (n = 155) predisposing (hereditary, acquired or circumstantial) risk factors for venous thrombosis. Factor V Leiden and prothrombin G→A²⁰²¹⁰ are known risk factors for venous thrombosis. After stratification for FV Leiden and prothrombin A²⁰²¹⁰ mutations, a significant association was also observed. After adjustment for sex, FV Leiden and prothrombin A²⁰²¹⁰ mutation, the estimated risk of venous thrombosis among carriers of the TT MTHFR genotype was 1.7 (95% CI: 1.2-2.6). The TT MTHFR genotype is independently associated with venous thrombosis, mainly among individuals with a high risk profile.

Full Text

References

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