Genetic variations observed in arterial and venous thromboembolism - Relevance for therapy, risk prevention and prognosis

• Main Authors: Harrington, D J, Malefora, A, Schmeleva, V, Kapustin, S, Papayan, L, Blinov, M, Harrington, P, Mitchell, M, Savidge, G F
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2003
• Subjects: North-Western Russia
• Online Access: https://kclpure.kcl.ac.uk/portal/en/publications/genetic-variations-observed-in-arterial-and-venous-thromboembolism--relevance-for-therapy-risk-prevention-and-prognosis(b4f685d3-0b8b-426c-bd47-1f3f6306406a).html; http://www.scopus.com/inward/record.url?scp=0038059033&partnerID=8YFLogxK

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 genelife 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/ 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.