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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2924-2929.)
© 1997 American Heart Association, Inc.

Articles

Hyperhomocyst(e)inemia and a Common Methylenetetrahydrofolate Reductase Mutation (Ala²²³Val MTHFR) in Patients With Inherited Thrombophilic Coagulation Defects

Cristina Legnani; Gualtiero Palareti; Francesca Grauso; Simonetta Sassi; Gabriele Grossi; Sandro Piazzi; Francesco Bernardi; Giovanna Marchetti; Paolo Ferraresi; ; Sergio Coccheri

From the Department of Angiology and Blood Coagulation (C.L., G.P., F.G., S.S., S.C.) and the Central Laboratory (G.G., S.P.), University Hospital S. Orsola-Malpighi, Bologna; and Dipartimento di Biochimica e Biologia Molecolare, Centro di Studi Biochimici delle Patologie del Genoma Umano, Università di Ferrara (F.B., G.M., P.F.), Italy.

Correspondence to Dr Cristina Legnani, Department of Angiology and Blood Coagulation, University Hospital S. Orsola, Via Massarenti, 9, 40138 Bologna, Italy.

Abstract To assess whether certain abnormalities of the sulfated amino acid metabolism are associated with the occurrence of thromboembolic events in patients with inherited thrombophilic conditions, the levels of homocyst(e)ine, before or after methionine load, and the presence of the Ala²²³Val substitution in the 5,10-methylenetetrahydrofolate reductase (MTHFR) were evaluated in 119 subjects with a congenital single thrombophilic condition (type I deficiency of antithrombin n=10, protein C n=24, protein S n=16; activated protein C resistance due to factor V Leiden mutation n=69). Sixty-three subjects had experienced at least one documented thrombotic event, while the remaining 56 subjects were still free from any thrombotic symptom. Our results show that (1) high homocyst(e)ine levels, either in fasting condition or after methionine load, were not more frequent in subjects with inherited thrombophilic alterations (14.4%) than in normal control subjects (10% by definition) and (2) the frequency of hyperhomocyst(e)inemia was similar in thrombophilic subjects, who already have (14.3%) or have not (14.6%) experienced thrombotic events. As regards the MTHFR mutation, the homozygous condition was present in 23.2% of the thrombophilic patients versus 17.5% in the control subjects, a nonsignificant difference. The mutation was slightly more frequent in those thrombophilic subjects who had suffered a thrombotic episode (25.5%) versus those with no thrombosis (20.8%), with odds ratios of 1.61 (confidence interval (CI)=0.58-4.52) and 1.24 (CI=0.42-3.43), respectively. These differences were also nonsignificant. It is concluded that in subjects with inherited thrombophilias, a condition of hyperhomocyst(e)inemia "per se" is not a factor increasing the risk of thrombosis. The risk enhancement conferred by the MTHFR mutation, if any, seems to be slight or limited, and its significance could be ascertained only in a large multicenter trial.

Key Words: hyperhocyst(e)inemia • thrombophilia • venous thrombosis • MTHFR mutation

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