MTHFR, MTR, and MTHFD1 gene polymorphisms compared to homocysteine and asymmetric dimethylarginine concentrations and their metabolites in epileptic patients treated with antiepileptic drugs

PURPOSE The purpose of the study was to determine the frequency of occurrence of polymorphisms of genes MTHFR (C677T), MTR (A2756G), and MTHFD1 (G1958A), as well as to analyze the concentration of homocysteine (Hcy), methionine (Met), asymmetric dimethylarginine (ADMA), and arginine (Arg) in epileptics treatment with antiepileptic drugs (AEDs), and controls. METHOD The study included 65 epileptic patients treated with variable AEDs and 61 controls. The levels of Hcy and Met were determined by HPLC/EC, ADMA and Arg by HPLC with fluorescence detection. Polymorphisms of the studied genes were determined by PCR-RFLP. RESULTS The study demonstrates that AEDs treatment in epileptics leads to increase in Hcy (p<0.05) and ADMA (p<0.01) concentrations. Greater increases in Hcy concentration during AEDs treatment appear to occur in individuals with the MTHFR CT (C677T) and MTHFD1 GG (G1958A) genotypes. Genetic conditions also appear to be related with changes in the ratios of Hcy, Met, Arg, and ADMA. It seems that in cases of AEDs treatment's effect on hyperhomocysteinemia, epileptic individuals appear to have a disturbed control of Hcy over ADMA. CONCLUSIONS It is possible, that polymorphisms of genes related to Hcy-to-Met metabolism, in epileptics treated with AEDs may have an effect on the regulation of levels of risk factors of vascular diseases, Hcy and ADMA.