Methylenetetrahydrofolate reductase C677T genotype and venous thromboembolic disease

Background: Many studies have suggested an increased risk of venous thromboembolism (VTE) in patients with mild hyperhomocysteinemia. The C677T mutation in the MTHFR gene has recently been described as a cause of mild hyperhomocysteinemia. Objectives: To investigate the potential of the C677T mutation in the MTHFR gene in its homozygous state as a risk factor for VTE. Methods: Case-control study design. The presence of the mutation was determined in all consecutive patients referred from July 1994 to September 1997 and in whom the diagnosis was duly confirmed. Analysis was carried out in a subgroup of VTE patients free from both acquired and genetic risk factors (factor-V mutation and/or prothrombin gene mutation). A control group consisted of 105 volunteer blood donors. Results: In the 366 patients with a confirmed VTE, 253 presented acquired risk factors and 58 were carriers of the factor-V Leiden mutation and/or G20210A mutation of the prothrombin gene. in the remaining 55 patients, VTE was considered as 'unexplained', and the frequency of the C677T mutation MTHFR was 21.8% in its homozygous state and 34.5% in its heterozygous state. in the control group, 9.5% were found homozygous and 34.3% heterozygous. The odds ratio for having VTE in the presence of the mutation in its homozygous state was 2.9 (95% CI 1.0-8.6). Conclusion: This study suggests that the homozygous C677T mutation in the MTHFR gene might be a risk factor of VTE in patients with spontaneous events and without other common genetic risk factors. Copyright (C) 2000 S. Karger AG, Basel.