A high frequency of the MTHFR 677C>T polymorphism in Scottish women with epilepsy: Possible role in pathogenesis

Summary The inheritance of most forms of epilepsy is usually considered to be multifactorial, although a number of single gene causes are known. Most previous studies of epilepsy genetics have implicated ion channel genes or ligand receptors. In a previous study of children with adverse effects of prenatal exposure to antiepileptic drugs, we noted an increased frequency of the methylene tetrahydrofolate reductase ( MTHFR ) 677C>T polymorphism in the mothers. To investigate this further, a new cohort of women with epilepsy has been identified from maternity hospital records and genotyped for polymorphisms in MTHFR , serine hydroxymethyl transferase ( SHMT1 ), methionine synthase ( MTR ) and methionine synthase reductase ( MTRR ). Healthy blood donors were genotyped as controls. The frequency of the MTHFR 677TT genotype was significantly higher in women with idiopathic generalised epilepsy than in healthy controls ( p = 0.012, OR 2.26, 95%CI 1.13–4.51). No association was detected for the other polymorphisms tested. The MTHFR 677C>T polymorphism may be a susceptibility factor for epilepsy, and its higher frequency in women with epilepsy may contribute to the increased risk of malformation in children of women with epilepsy.