Venous Thromboembolic Disease and the Prothrombin, Methylene Tetrahydrofolate Reductase and Factor V Genes
Martine Alhenc-Gelas, Emmanuel Arnaud, Viviane Nicaud, Marie-Laurence Aubry, Jean-Noël Fiessinger, Martine Aiach, Joseph Emmerich
From Unité INSERM 428, Unité INSERM 258, and Centre Claude Bernard de Recherche sur les Maladies Vasculaires, Hôpital Broussais – AP-HP, Paris, France
Summary The prevalence of the A20210 allele of the prothrombin (PT)gene and the T677 allele of the methylene tetrahydrofolate reductase(MTHFR) gene was determined in 205 patients with venousthromboembolism (VTE) and in 398 healthy subjects of similar ageand sex distribution. We also determined the frequency of these twocandidate risk alleles in subjects carrying the factor V (FV) Q506allele, to identify a possible interaction. Forty patients (19.5%) and 14control subjects (3.5%) were heterozygous for the FV R506Q mutation.Twenty-one patients (10.2%) and 11 controls (2.8%) were heterozygousfor the PT A20210 allele (odds ratio (OR) 4.02, 95% confidenceinterval (CI): 1.90-8.50, p < 0.001). This confirmed that the PT A20210allele was a risk factor for VTE in our population. Among the FV Q506allele carriers, 9 patients (22.5%) and no control also had the PT geneG20210A mutation. The absence of the combined abnormality in thecontrol group made it impossible to calculate the relevant ORs but thelower bound of the 95% CI was 3.94, suggesting that individualsbearing the two mutations have a higher risk than those with a singlemutation. Twenty-six patients (12.7%) and 49 controls (12.3%) werehomozygous for the MTHFR T677 allele (OR 1.04, 95% CI: 0.62-1.72,not significant). Four patients and 1 control were also heterozygous forthe FV R506Q mutation (OR 9.33, 95% CI: 1.03-84.23). However,the ORs for carriers of the FV R506Q mutation were not significantlyinfluenced by MTHFR gene C677T homozygosity.