Hyperhomocysteinemia, Low Folate and Vitamin B 12 Concentrations, and Methylene Tetrahydrofolate Reductase Mutation in Cerebral Venous Thrombosis

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Abstract
Background and Purpose— Elevated plasma levels of homocysteine are associated with an increased risk of deep-vein thrombosis. Through a case–control study, we examined the potential association among homocysteine, folate and vitamin B 12 levels, and the common C677→T mutation in the methylene tetrahydrofolate reductase ( MTHFR ) gene in patients with cerebral venous thrombosis (CVT). Methods— Forty-five patients with CVT and 90 control subjects were studied. Plasma levels of homocysteine (fasting and after methionine load), folate, and vitamin B 12 were measured. Genotyping of the MTHFR gene was also performed. The estimated risk of CVT associated with hyperhomocysteinemia, low vitamin levels, and MTHFR mutation were expressed as odds ratio (OR) and its 95% CI (crude and after adjusting by other independent variables). Results— The adjusted OR for CVT associated with high (>90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant ( P =0.098). Patients with MTHFR mutation and low folate levels presented the highest homocysteine levels. Conclusions— High plasma concentrations of homocysteine and low plasma folate levels were associated with an increased risk of CVT in this population in which low socioeconomic conditions and deficient nutritional status may contribute to its relatively high incidence.