MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous Thromboembolism: A Retrospective Chart Review Study

Abstract

Background: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine metabolism. This study aims to determine the impact of MTHFR polymorphisms on plasma homocysteine levels and risks of venous thromboembolism (VTE). Methods: This retrospective chart review study included a total of 188 subjects who were tested for MTHFR polymorphisms at Metrowest Coagulation Laboratory between April 2011 and April 2016. Two independent coders were trained to extract relevant clinical data for statistical analysis. Results: VTE occurred in 50% of patients with compound mutation, compared with only 28.6% of subjects from the wild-type group. Patients with heterozygous or homozygous A1298C or C677T variants had an intermediate risk of VTE. The median homocysteine level in the wild-type group was slightly lower than that of heterozygous or homozygous MTHFR variants. The difference, however, was not significant (p = 0.6193). Moreover, there was no difference in plasma homocysteine level between patients with VTE versus VTE-free (p = 0.4923). Conclusions: Heterozygous or homozygous MTHFR variants, especially a compound mutation, are associated with increased risk of VTE. Hyperhomocysteinemia does not correlate with MTHFR polymorphisms or VTE risk. Hence, MTHFR genotyping provides more consistent assessment of VTE risk. This information can be incorporated into risk stratification for early intervention and prophylaxis of VTE.

Molecular Analysis of Prothrombotic Gene Variants in Venous Thrombosis: A Potential Role for Sex and Thrombotic Localization

“…Similarly, FXIII V34L, beta-fibrinogen -455, HPA-1, MTHFR C677T and A1298C variants and PAI-1 4G/5G alleles did not demonstrate a relationship with VTE [21]. At variance with the present data are previous studies that found MTHFR A1298C alone [22] or in combination with the C677T variant to be associated with VTE [23]. Likewise, a significant increase in the PAI-1 4G allele frequency was found in VTE patients who also had FVL [24].…”

“…In agreement with previous reports [28,29], our results show a significantly higher than normal frequency of FII G20210A in patients with cerebral venous thrombosis. At variance with older data [22,23], however, the presented data rule out a role for MTHFR and FVL variants in CVT. Interestingly, in CVT (as we observed in PVT), the frequency of FII G20210A is higher in females than in males.…”

Molecular analysis of prothrombotic gene variants in venous thrombotic diseases. Different risk factors in different sex and clinical forms.

“…[25]. While, differently from our study, MTHFR A1298C and C677T variants were found as risk factors for VTE [26]; and another study [27] revealed that only the MTHFR A1298C but not the C677T MTHFR variant was a risk factor for VTE. A significant increase of the PAI-1 4G allele frequency was found only in VTE patients that had also the FVL [28].…”

Genetic association study of fatal pulmonary embolism

“…Associations of the A1298C (rs1801131) and C677T (rs1801133) variants of the MTHFR gene and an increased VTE risk were found by Liu et al [46]. Brandimarti et al [21] examined these two polymorphisms but their results did not demonstrate significant differences of the polymorphisms in cases and controls.…”