HYPERHOMOCYST(E)INEMIA AND A COMMON METHYLENETETRAHYDROFOLATE REDUCTASE MUTATION (ALA(223)VAL MTHFR) IN PATIENTS WITH INHERITED THROMBOPHILIC COAGULATION DEFECTS

To assess whether certain abnormalities of the sulfated amino acid met abolism are associated with the occurrence of thromboembolic events in patients with inherited thrombophilic conditions, the levels of homoc yst(e)ine, before or after methionine load, and the presence of the Al a(223)Val substitution in the 5,10-methylenetetrahydrofolate reductase (MTHFR) were evaluated in 119 subjects with a congenital single throm bophilic condition (type I deficiency of antithrombin n=10, protein C n=24, protein S n=16; activated protein C resistance due to factor V L eiden mutation n=69). Sixty-three subjects had experienced at least on e documented thrombotic event, while the remaining 56 subjects were st ill free from any thrombotic symptom. Our results show that (1) high h omocyst(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 throm bophilic subjects, who already have (14.3%) or have not (14.6%) experi enced thrombotic events. As regards the MTHFR mutation, the homozygous condition was present in 23.2% of the thrombophilic patients versus 1 7.5% in the control subjects, a nonsignificant difference. The mutatio n was slightly more frequent in those thrombophilic subjects who had s uffered 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 non significant. It is concluded that in subjects with inherited thromboph ilias, a condition of hyperhomocyst(e)inemia ''per se'' is not a facto r increasing the risk of thrombosis. The risk enhancement conferred by the MTHFR mutation, if any, seems to be slight or limited, and its si gnificance could be ascertained only in a large multicenter trial.