RESUMEN
We undertook genetic and biochemical assays in patients with arterial (n = 146) and venous (n = 199) thromboembolism and survivors of pulmonary embolism (n = 58) to study causation and gene-life style interactions. In the clinical material from North Western Russia, factor V Leiden was found to be a risk factor in venous thrombosis (OR = 3.6), while the methylenetetrahydrofolate reductase (MTHFR) C677T mutation was a significant variable in both venous (p = 0.03) and arterial thrombosis (p = 0.004). Homocysteine levels were determined (n = 84) and hyperhomocysteinemia correlated with the T allele of the MTHFR gene, and with smoking and coffee consumption. Vitamin supplementation reduced homocysteine levels dependent on MTHFR genotype (36% TT, 25% CT, 22% CC). In pulmonary embolism patients, frequency of the -455G/A beta-fibrinogen dimorphism was studied. Carriers of this allele were significantly underrepresented (p < 0.02) among pulmonary embolism survivors (34.5%) compared to controls (56.7%). Additionally, -455AA homozygotes were found in 11.7% controls but only 1.7% of pulmonary embolism patients (p = 0.006). In venous and arterial thrombosis cases, MTHFR and homocysteine data led to effective dietary supplementation with a reduced risk of disease progression. Results from the pulmonary embolism study may indicate that screening tests for the -455G/A beta-fibrinogen genetic variation could be of prognostic value, and may point the way for novel anticoagulation strategies.
Asunto(s)
Arteriopatías Oclusivas/genética , Factor V/genética , Variación Genética/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Protrombina/genética , Tromboembolia/genética , Trombosis de la Vena/genética , Adulto , Arteriopatías Oclusivas/enzimología , Análisis Mutacional de ADN , Cartilla de ADN/química , Femenino , Fibrinógeno/genética , Genotipo , Humanos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , Tromboembolia/enzimología , Trombosis de la Vena/enzimologíaRESUMEN
We report a patient with unusual venous and arterial thromboses in association with the common thermolabile methyltetrahydrofolate (MTHFR) variant. The patient responded directly to folate supplementation. To our knowledge, this is the first report describing hyperhomocysteinemia in association with this type of thrombosis.