Hyperhomocysteinemia increases the risk of venous thrombosis independent of the C677T mutation of the methylenetetrahydrofolate reductase gene in selected Brazilian patients

Abstract

Fasting total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation were evaluated in 91 patients with venous thromboembolism and without acquired thrombophilia, and in 91 age-matched and sex-matched controls. Hyperhomocysteinemia was detected in 11 patients (12.1%) and in two controls (2.2%), yielding an odds ratio (OR) for venous thrombosis of 6.1 [95% confidence interval (CI), 1.3-28.4]. After excluding 21 patients and four controls with other known genetic risk factors for venous thrombosis, the OR was not substantially changed (7.0; 95% CI, 1.5-33.1). The prevalence of the MTHFR 677TT genotype was not significantly different in patients (9.9%) and in controls (5.5%), with an OR for venous thrombosis of 1.8 (95% CI, 0.6-5.8). Subjects with the MTHFR 677TT genotype showed higher levels of tHcy compared with the 677CC genotype in patients (P = 0.010) and in controls (P = 0.030). In conclusion, we found that fasting hyperhomocysteinemia is a risk factor for venous thrombosis in patients without known acquired thrombophilia and other genetic risk factors for venous thrombosis. Although tHcy levels are significantly higher in those homozygous for the MTHFR C677T mutation, this genotype does not increase the thrombotic risk in our study population.

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

“…19 In our study, in which patients were re-examined 1 to 18 years after the first DVT episode (median five years), we observed a high rate of DVT recurrence: 36% and 32% in the TG and CG respectively. Four thrombophilic patients had rethrombosis while on increasing the risk of thrombotic events by five to ten times in heterozygotic carriers and more than ten times in homozygotic patients, 6,11 especially in association with other risk factors such as advanced age (over 65) or oral contraceptive use, 7,9,15,29 which was the second most common risk factor in our patient sample.…”

“…12,13 The G20210A polymorphism of the prothrombin gene is associated with increased plasma prothrombin levels and is present in 1 to 3% of individuals in the general population and 6 to 18% of patients with VTE. 14 While the methylenetetrahydrofolatereductase mutation (MTHFR) does not itself appear to be a risk factor for DVT, 15 it may be associated with hyperhomocysteinemia. 16 Antiphospholipid syndrome (APS) is an acquired thrombophilia, characterized by the occurrence of venous thrombosis and/or arterial thrombosis and/or recurrent miscarriages in the presence of laboratory evidence of antiphospholipid antibodies.…”

Nutritional Factors, Homocysteine and C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene in Algerian Subjects with Cardiovascular Disease

“…This observation is consistent with other studies. One such study (43) found no association between the plasma tHCY and the MTHFR mutation, although in a meta-analysis, Klerk et al (44) found that the MTHFR 677TT genotype was associated with elevated tHCY level. However, most studies did not show an association between the MTHFR mutation and subsequent development of CVD (45)(46)(47).…”

Homocysteine reduction by B‐vitamin supplementation increases t‐PA and PAI‐1 levels in patients with venous thromboembolism

“…Extrahepatic portal vein thrombosis (PVT) is an infrequent but serious condition. Major causes of PVT in adults are cirrhosis, malignancy and local major inflammation, which by impediment of portal vein blood flow promote thrombosis [1][2][3]. The term idiopathic PVT has been coined to label cases with no apparent cause.…”

“…Homocysteine reduction by B-vitamin supplementation increases t-PA and PAI-1 levels in patients with venous thromboembolism Elevated homocysteine levels are associated with an increased risk of cardiovascular disease and venous thromboembolism (VTE), as demonstrated by case-control and prospective studies [1][2][3]. Experimental studies have shown that homocysteine may damage the endothelium and enhance thrombogenicity by stimulating procoagulant pathways and impairing anticoagulant and fibrinolytic pathways [4].…”