SummaryThe 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 venous thromboembolism (VTE) and in 398 healthy subjects of similar age and sex distribution. We also determined the frequency 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 mutation. 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 factor for VTE in our population. Among the FV Q506 allele carriers, 9 patients (22.5%) and no control also had the PT gene G20210A mutation. The absence of the combined abnormality in the control group made it impossible to calculate the relevant ORs but the lower bound of the 95% CI was 3.94, suggesting that individuals bearing the two mutations have a higher risk than those 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 the FV R506Q mutation (OR 9.33, 95% CI: 1.03-84.23). However, the ORs for carriers of the FV R506Q mutation were not significantly influenced by MTHFR gene C677T homozygosity.

Abstract-We analyzed the distal promoter region of the thrombomodulin (TM) gene (nucleotides Ϫ300 to Ϫ2052) in subjects from the Paris Thrombosis Study (PATHROS), a French case-control study of venous thrombosis, to identify polymorphisms that might modify TM gene expression. Eight novel mutations were found in the 40 DNA samples initially screened. Two of these mutations (Ϫ1748G/C and Ϫ1208/Ϫ1209 del TT) were frequent. One rare transition (Ϫ1166G/A) might have functional consequences owing to its position. These 3 mutations were screened for in the entire study population of 327 patients and 398 controls. None of the 3 was significantly associated with thrombosis. Interestingly, the Ϫ1208/Ϫ1209 TT deletion was associated with varicose veins in the patients. This mutation was in tight linkage disequilibrium with the ϩ1418 C/T change in the coding sequence, a known polymorphism that predicts an

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