Hyperhomocysteinemia is a frequent risk factor for
deep-vein thrombosis. A common mutation (C677T) in the gene encoding for
methylenetetrahydrofolate reductase (MTHFR) is responsible, in the homozygous state, for decreased
enzyme activity and mild
hyperhomocysteinemia and is associated with increased risk for
cardiovascular disease. We studied the prevalence of C677T MTHFR in 77 patients with
deep-vein thrombosis and in 154 age- and sex-matched healthy control subjects. In the same individuals, we also evaluated the frequency of the coexistence of C677T MTHFR with mutant
factor V:Q506, a common risk factor for
deep-vein thrombosis. Sixteen patients (20.8%) and 35 control subjects (22.7%) were homozygous for the C677T MTHFR mutation (odds ratio [OR] = 0.8, 95% confidence interval [CI] = 0.4-2.0). Sixteen patients (20.8%) and 4 control subjects (2.6%) had
factor V:Q506; of them, 10 patients and 3 control subjects had isolated
factor V:Q506 (adjusted OR = 6.3, 95% CI = 1.6-25.3) and 6 patients and 1 control subject also had C677T MTHFR (adjusted OR = 17.3, 95% CI = 2.0-152.9). The OR for the coexistence of the two mutations was 65% to 75% higher than the expected joint effect calculated by either an additive (OR = 6.0) or multiplicative (OR = 4.4) model. The homozygous C677T mutation of MTHFR per se is not a risk factor for
deep-vein thrombosis but increases the risk associated with
factor V:Q506. Due to the high prevalence of C677T MTHFR, it is likely that previous studies, which did not look for this mutation, overestimated the relative risk of
thrombosis associated with
factor V:Q506 alone.