Genetic variations observed in arterial and venous thromboembolism--relevance for therapy, risk prevention and prognosis.
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.
Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London, UK.
Dominic J
DJ
Harrington
Agata
A
Malefora
Veronika
V
Schmeleva
Sergey
S
Kapustin
Ludmila
L
Papayan
Mikhail
M
Blinov
Pip
P
Harrington
Mike
M
Mitchell
Geoffrey F
GF
Savidge
D000328:Adult; D001157:Arterial Occlusive Diseases / Q000201:enzymology / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005165:Factor V / Q000235:genetics*; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011516:Prothrombin / Q000235:genetics*; D013923:Thromboembolism / Q000201:enzymology / Q000235:genetics*; D020246:Venous Thrombosis / Q000201:enzymology / Q000235:genetics*
D017931:DNA Primers; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D005340:Fibrinogen; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)