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

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 C6773 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 (Ͼ90th percentile) fasting levels of homocysteine was 4.6 (1.6 to 12.8). The association between low plasma folate values (Ͻ10th percentile) and presence of CVT was 3.5 (1.2 to 10.0) after adjustment for confounding factors. There was a higher frequency of MTHFR mutation in patients with CVT (22% versus 10%), but it was not statistically significant (Pϭ0.098). 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.

Evaluation of risk factors for thrombophilia in patients with cerebral venous thrombosis

“…In our study, CVT did not develop during the gestation or puerperal period in female cases. In populations with low folate levels and low socioeconomic status, mutation in the MTHFR gene and hyperhomocysteinemia increase the risk for IS [9,10,15,25]. In a study performed on 125 patients by Nadir et al [27], there was no correlation between high plasma homocysteine levels and C677T mutation in the MTHFR gene.…”

“…They did not observe significant differences in the prevalence of thrombophilia between cases and control subjects or between pathogenic subtypes of IS. In another case-control study reported by Cantu et al [25], the potential association among homocysteine, folate and vitamin B12 levels and the common C677T mutation in the MTHFR gene was examined in patients with CVT. The authors also performed thrombophilic tests and reported a higher prevalence of APC-R and presence of FVL and mutation in the PT gene (G20210A) in CVT patients [25].…”

“…In another case-control study reported by Cantu et al [25], the potential association among homocysteine, folate and vitamin B12 levels and the common C677T mutation in the MTHFR gene was examined in patients with CVT. The authors also performed thrombophilic tests and reported a higher prevalence of APC-R and presence of FVL and mutation in the PT gene (G20210A) in CVT patients [25]. In another study conducted in patients with CVT [26], infections and postpartum state were found to be the most common predisposing factors for CVT, and the prevalence of genetic thrombophilia was 5%.…”

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

“…Homocysteine (Hcys) is a non-essential, sulfur-containing amino acid formed during the metabolism of methionine. Mild hyperhomocysteinemia (hHcys), which occurs in approximately 5-7% of the general population, has been proved to be thrombogenic and an independent risk factor for coronary artery disease [20] , arterial and venous thrombosis [21][22][23][24][25][26] . Elevated levels of Hcys may result from abnormalities in metabolism pathways due to inherited abnormalities of the enzymes involved or nutrient deficiencies such as insufficiency of folate and vitamins B 2 , B 6 , and B 12 [27,28] .…”

Cerebral Venous Sinus Thrombosis: Incidence and Hyperhomocysteinemia as a Risk Factor in Japanese Patients

“…Its incidence is about 0.5% to 1.0% among all types of stroke [1][2][3]. There are many risk factors of CVT [1][2][3]; genetic or acquired thrombophrenia and oral contraceptive use are the most common risk factors, and hyper-homocysteinemia (Hcy) is an additional risk factor [4][5][6][7][8]. A meta-analysis of 17 clinical studies showed that oral contraceptive use, Leiden mutation of Factor V, and hyperHcy were recognized as statistically significant risk factors 8).…”