Venous thromboembolic disease and the prothrombin, methylene tetrahydrofolate reductase and factor V genes

The prevalence of the A20210 allele of the prothrombin (PT) gene and the T6 77 allele of the methylene tetrahydrofolate reductase (MTHFR) gene was dete rmined in 205 patients with venous thromboembolism (VTE) and in 398 healthy subjects of similar age and sex distribution. We also determined the frequ ency of these two candidate risk alleles in subjects carrying the factor V (FV) Q506 allele, to identify a possible interaction. Forty patients (19.5% ) and 14 control subjects (3.5%) were heterozygous for the FV R506Q mutatio n. Twenty-one patients (10.2%) and 11 controls (2.8%) were heterozygous for the PT A20210 allele (odds ratio (OR) 4.02, 95% confidence interval (CI): 1.90-8.50, p <0.001). This confirmed that the PT A20210 allele was a risk f actor for VTE in our population. Among the FV Q506 allele carriers, 9 patie nts (22.5%) and no control also had the PT gene G20210A mutation. The absen ce of the combined abnormality in the control group made it impossible to c alculate the relevant ORs but the lower bound of the 95% CI was 3.94. sugge sting that individuals bearing the two mutations have a higher risk than th ose with a single mutation. Twenty-six patients (12.7%) and 49 controls (12 .3%) were homozygous for the MTHFR T677 allele (OR 1.04, 95% CI: 0.62-1.72, not significant). Four patients and 1 control were also heterozygous for t he FV R506Q mutation (OR 9.33, 95% CI: 1.03-84.23). However, the ORs for ca rriers of the FV R506Q mutation were not significantly influenced by MTHFR gene C677T homozygosity.