Antiepileptic Drugs and MTHFR Polymorphisms Influence Hyper‐Homocysteinemia Recurrence in Epileptic Patients

The influence of antiepileptic drugs (AEDs) and/or common polymorphisms (677C --> T, 1298A --> C) of the methylene-tetrahydrofolate-reductase (MTHFR) gene on the recurrence time of hyper-total-homocysteinemia (tHcy > 13 micromol/L) was investigated in 59 hyper-homocysteinemic patients (34M/25F, 20-49 years). Plasma tHcy and folate were assayed before and after 1-month folate supplementation (5 mg/day), and after 2, 4, and 6 months. Four MTHFR polymorphism groups were identified with the following tHcy (micromol/L) and folate (nmol/L) levels (mean +/- SD): (a) MTHFR677TT/1298AA, 24 patients, 36.0 +/- 4.8, 4.1 +/- 0.7; (b) MTHFR677CT/1298AC 27.1 +/- 2.7, 5.3 +/- 1.0 (n = 15); (c) MTHFR677CT/1298AA 16.6 +/- 3.6, 6.8 +/- 1.0 (n = 11), all taking enzyme-inducing AEDs; and (d) MTHFR677TT/1298AA 24.5 +/- 3.2, 5.6 +/- 1.1 (n = 9), treated with new AEDs. After folate therapy, plasma t-Hcy and folate were normal in all patients. At 6 months, 43 patients (72.9%) exhibited hyper-tHcy, the greater proportion belonging to the EI-AED-MTHFR677TT/1298AA (39%). Knowledge of the hyper-tHcy recurrence time after folate therapy discontinuation may help in optimizing folate supplementation pulses.