Abstracts

Thymidylate synthase(TS) gene encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuriylate to thymidylate, and contains a tandem repeat polymorphism, of which a triple repeat is associated with increased expression of TS. TS is key enzymes in the folate metabolism and compete with methylenetetrahydrofolate reductase(MTHFR) for limiting supplies of folate required for the remethylation of homocysteine. We studied to clarify the association between these genetic variations and prognosis in epilepsy. A total of 125 epilepsy patients was included. All patients have been medicated with antiepileptic drug over at least one year. We investigated the TS promoter 28 bp polymorphism in serum of epilepsy patients using PCR amplification of genomic DNA. We obtained 2 different DNA fragments, which indicated triple-repeat (3R) and double-repeat (2R) type alleles. 68% of patients with epilepsy were 3R3R, 30.4% were 2R3R, 1.6% were 2R2R. In seizure frequency during one-year with medication, 3R3R was 7.94/year, 2R3R and 2R2R was 1.85/yr. Combined analysis of TS and MTHFR polymorphisms(C677T) revealed that CT/3R3R and TT/3R3R increase seizure frequency. Epilepsy patients who were homozygous for the triple repeat had a poorer prognosis than those with other genotypes, especially when combined with mutant alle for MTHFR. So, our results suggest that the genotyping for the TS polymorphisms may become a useful indicator in determining prognosis of epilepsy.