The risk of venous thromboembolism associated with the factor V Leiden mutation and low B-vitamin status.
Venous thromboembolism (VTE) is a multi-factorial disease involving numerous genetic and environmental risk factors. In this study we investigated the occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and low folate and vitamin B12 levels in young patients with thrombosis. We studied 78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age 44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated in all subjects. Factor V Leiden was highly prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous in controls). An increase in the risk of idiopathic VTE was associated with Hcy levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR = 7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin B12 were independently and strongly associated with the risk of VTE in a multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76, respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels of vitamin B12, compared to 28% of patients who were non-carriers of the mutation (p = 0.03). In contrast, none of the control carriers of the mutation had a low level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12 and folate was stronger than that introduced by elevated Hcy levels. The increased risk of VTE, accompanied by factor V Leiden, may be related to confounding environmental factors.
Department of Clinical Chemistry, Saarland Medical School, Homburg, Germany.
Rima
R
Obeid
Tarek
T
Hakki
Muhidien
M
Jouma
Wolfgang
W
Herrmann
D005165:Factor V / Q000235:genetics*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009154:Mutation; D013923:Thromboembolism / Q000150:complications / Q000235:genetics*; D020246:Venous Thrombosis / Q000150:complications / Q000235:genetics*; D014804:Vitamin B Deficiency / Q000150:complications*
C095381:factor V Leiden; D005165:Factor V; D042965:Methylenetetrahydrofolate Reductase (NADPH2)