Background: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (HCY) metabolism. Previous studies have demonstrated that homozygosis for the MTHFR C677T mutation is associated with an increased risk of thrombosis, even in the absence of hyperhomocysteinemia (hHCY). However, this relationship remains controversial.
Aims: To determine the incidence of thrombosis in patients homozygous for C677T MTHFR mutation, with or without hHCY, compared to healthy individuals with the same characteristic; we divided the patients into two groups: those with normal HCY levels and those with hHCY, assessing the incidence of thrombosis in both groups. The data obtained from the two groups were analyzed using chi-square test
Methods: We retrospectively analysed the clinical data of 570 subjects with homozygosity for the C677T MTHFR mutation followed by our centre in the last 10 years: 149 males, 421 females; average age: 39.7 (4-88). 382 had normal HCY and 188 had hHCY. All subjects with other congenital or acquired thrombophilia states were excluded from the study. hHCY has been defined if greater than 15 micromol/L.
Results:
| Homozygous C677T MTHFR patients with thrombosis |
Homozygous C677T MTHFR patients without thrombosis | |
| Normal Homocysteine (≤15 micromol/L) and % (n=382) | 57 (14.9%) | 325 (85.1%) |
| High Homocysteine (>15.1 micromol/L) and % (n=188) |
29 (15.4%) | 159 (84.6%) |
| Total: 570 | 86 (15.1%) | 484 (84.9%) |
Table 1: Incidence of thrombosis in homozygous C677T MTHFR patients with and without hyperhomocysteinemia.
We found very similar incidence of thrombosis in homozygous subjects with hHCY, 29/188 (15.4%), compared to those with normal homocysteine, 57/382 (14.9%). The results showed statistical significance by Chi-square test: X2 (1, N = 570) = 0.025, p = .874398. Data are summarized in table 1.
Conclusions: Unlike other authors, our data did not confirm the importance of hHCY as an independent thrombotic risk factor; the incidence of thrombosis in C677T MTHFR homozygotes also appears to be lower than that shown in the literature. Prospective and randomized studies, especially in comparison to subjects without MTHFR mutations, are necessary to understand better the real prothrombotic role of C677T MTHFR and hHCY.
To cite this abstract in AMA style:
Nicolò GM, Sottilotta G, Luise F, Oriana V, Piromalli A. Incidence of Thrombosis in Patients with MTHFR C677T Homozygosity and Hyperhomocysteinemia [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/incidence-of-thrombosis-in-patients-with-mthfr-c677t-homozygosity-and-hyperhomocysteinemia/. Accessed August 15, 2022.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/incidence-of-thrombosis-in-patients-with-mthfr-c677t-homozygosity-and-hyperhomocysteinemia/