Common C677T Polymorphism of the Methylenetetrahydrofolate Reductase Gene and the Risk of Venous Thromboembolism: Meta-Analysis of 31 Studies

Abstract

Background: Although the common 677 C → T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene is implicated in the development of hyperhomocysteinemia, its correlation with venous thromboembolism (VTE) remains controversial. We conducted a meta-analysis of previously published studies to clarify the role of the MTHFR 677 TT homozygous genotype in association with VTE. Methods and Results: Relevant articles were retrieved from a systematic search of Medline and Embase from 1990 to September 2001. Two independent reviewers abstracted data on the characteristics of the cases with VTE and controls without VTE. We pooled the rates of the MTHFR 677 TT genotype in both groups, as well as the odds ratio (OR) of VTE in the presence of the TT versus CC or CT genotypes. In 31 published studies, comprising 4,901 cases and 7,886 controls, the pooled prevalence of the MTHFR 677 TT genotype was slightly higher among cases (14.3%) than controls (11.7%), conferring a borderline degree of heightened risk [pooled OR (OR_p) 1.2, 95% confidence interval (CI) 1.1–1.4]. After excluding cases with a classic thrombophilia factor, the pooled prevalence rates of the MTHFR 677 TT genotype among 11 studies were 17.7 and 12.3%, respectively (OR_p 1.5, 95% CI 1.2–1.9). Conclusions: The classic MTHFR C677T gene polymorphism is weakly associated with an increased risk of VTE. It is unlikely that the purported relationship between hyperhomocysteinemia and VTE is mediated by this gene defect to a substantial degree, although other undiscovered gene polymorphisms may explain this association. Until more compelling data are made available, we do not recommend that testing for the MTHFR C677T polymorphism be routinely included as part of any clinical thrombophilia assessment.

The Importance of Homozygous Polymorphisms of Methylenetetrahydrofolate Reductase Gene in Romanian Patients with Idiopathic Venous Thromboembolism

“…The prevalence in Southeastern Europe countries are 45%, 43%, 40%, in Hungary, Ukraine, Russia, respectively (5,26). Although a study performed in Germany showed a 2.12 increased risk of DVT for individuals with the heterozygous genotype, found in 43.8% of patients, the majority of studies showed no association with VTE, concordant with our results (33,(35)(36)(37)(38)(39)(40).…”

“…26 (24,29,33,35,36) and a 20% increased risk of VTE (37), whereas other studies failed to reveal any significant association (25,(38)(39)(40). Previous Romanian studies regarding thrombophilia in obstetric cases detected frequencies of the homozygous MTHFR 677TT genotype of 19.4% and 19.56% in pregnant patients with haemorrhagic complications and in patients with repetitive spontaneous abortions; no significant associations were found, except for a slightly increased risk for repetitive abortions in the presence of this genotype (41,42).…”

C677T methylenetetrahydrofolate reductase gene polymorphism as a risk factor involved in venous thromboembolism: A population-based case-control study

“…An MTHFR 677TT genotype was not significantly associated with VTE (OR, 1.13; 95% CI, 0.70-1.81). Ray et al (28) reported that the classic MTHFR C677T gene polymorphism is weakly associated with an increased risk of VTE. It is unlikely that the purported correlation between hyperhomocysteinemia and VTE is mediated by this gene defect to a substantial degree, although other unidentified gene polymorphisms may explain this association.…”

Hyperlipoproteinemia(a) and Hyperhomocysteinemia in an Young Female with Cerebrovascular Accident

“…These patients are considered milder homozygotes/ heterozygotes for cystathione beta synthase or methylene tetrahydrofolatereductase (MTHFR) deficiency. 6,7 It has been found that homozygous MTHFR mutation is associated with various complications in pregnancy like preeclampsia, placental abruption, but whether recurrent pregnancy loss is associated or not, yet to be proved. 7 Though prospective randomized controlled trial of lowering serum homocysteine levels with supplements of folic acid, vitamin B 6 & vitamin B 12 against a placebo over a 5 year period in patients with vascular disease or diabetes have not however shown any reduction in major cardiovascular events, 8 meta analysis has suggested that folic acid supplementation reduces the risk of stroke by 18%.…”