A second mutation in the methylenetetrahydrofolate reductase gene and the risk of venous thrombotic disease

We assessed the effect of a recently described mutation in the MTHFR gene (1298 A --> C) on the risk of deep venous thrombosis (DVT) by determining its prevalence in 190 patients with verified DVT and in age-, race- and gender-matched controls. MTHFR 1298 A --> C was found in 42.1% of patients and in 41.1% of controls. The OR for venous thrombosis was 1.07 (95% CI 0.70-1.65) for heterozygotes and 0.83 (95% CI 0.33-2.08) for homozygotes. The OR for the factor V Leiden (FVL) mutation was 3.40 (95% CI 1.22-9.48), for FII 20210 G --> A was 5.22 (95% CI 1.12-24.2) and for MTHFR 677 C --> T, 1.24 (95% CI 0.82-1.87). No significant increased risk for venous thrombosis was found when MTHFR 1298 A --> C was coinherited with FVL (OR 2.85, 95% CI 0.88-9.23), FIT 20210 G --> A (OR 7.19, 95% CT 0.87-59.4) or MTHFR 677 C --> T (OR 1.44, 95% CT 0.71-2.92). These data do not support a critical role of MTHFR 1298 A --> C in the predisposition to DVT.

Relationship between diet and anticoagulant response to warfarin - A factor analysis

Background Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. Aim of the study To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease. Methods Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K-1), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data. Results Mean age was 59 +/- 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3. Conclusion Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease.

The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis

Background and Objectives. A frequent mutation in the cystathionine beta-synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we Investigated this mutation as a candidate risk factor for venous thrombosis.Design and Methods. The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes, Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene.Results. The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C GBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co-inheritance of the two mutations.Interpretation and Conclusions. Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis. (C)1998, Ferrata Storti Foundation.

Effect of different glycosaminoglycans in a guinea-pig carotid-artery thrombosis model

Heparin is the most frequently used drug for the prevention and treatment of thrombosis. Its use, however, is restricted by its side-effects. To study the efficacy of other glycosaminoglycans that could substitute heparin in the management of arterial thrombosis, 60 guinea-pigs were randomly allocated into 6 groups: G1= control, G2= heparin (150 IU/kg), G3= heparan sulfate from beef pancreas (2.5 mg/kg), G4= heparan sulfate from beef lung (2.5 mg/kg), G5= N-acetylated heparan from beef pancreas, G6= dermatan sulfate from beef intestine (2.5 mg/kg). Ten minutes after intravenous injection of the drugs, thrombosis was induced by the injection of a 50% glucose solution into a segment of the right carotid artery isolated between 2 thread loops during 10 minutes. Three hours later the artery was re-exposed and if a thrombus was present it was measured, withdrawn and weighed. Thrombin time and activated partial thromboplastin time were measured in all animals. Thrombus developed in 90% of the animals in the control group, 0% in G2 and G3, 62.5% in G4, 87.5% in G5 and G6. Only in the animals treated with heparin the coagulation tests were prolonged. In conclusion, in the used dose only the heparan sulfate from beef pancreas presented an antithrombotic effect similar to heparin in this experimental model.