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

Summary:  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 μmol/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 (5mg/day), and after 2, 4, and 6 months. Four MTHFR polymorphism groups were identified with the following tHcy (μmol/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.