RESUMEN
PURPOSE: Thymidylate synthase (TS) gene encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a tandem repeat polymorphism, of which a triple repeat is associated with increased expression of TS. TS is a key enzyme 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 MTHFR C677T and TS polymorphism and prognosis in epilepsy. METHODS: 119 patients with antiepileptic drug more than one year were included. We investigated the MTHFR C677T and TS polymorphism using PCR, and analyzed the association between plasma homocysteine, folate levels, clinical profiles (especially seizure frequencies) and polymorphism. RESULTS: In seizure frequencies during one year, TT type in MTHFR and 3R3R type in TS polymorphism had higher frequencies than any other types without statistical significance. In plasma homocysteine levels, TT type had significantly higher homocsyteine levels than any other types, but 3R3R type had higher homocsyteine levels than any other types without statistical significance. Combined analysis of MTHFR C677T and TS polymorphism revealed that plasma homocysteine levels (18.22+/-8.32 micromol/l; p=0.039) and seizure frequencies (6.38+/-7.35/year; p=0.04) in patients with TT/3R3R were significantly higher than any other groups. A significant correlation between plasma homocysteine levels and seizure frequencies also was shown in multivariate linear regression analysis (B=0.160, Std error=0.069, adjusted R2=0.039, p=0.021). CONCLUSION: Epileptic patients with hyperhomocysteinemia, especially when combined with mutant allele for MTHFR and TS genes, have higher seizure frequencies. Therefore, our results suggest that the genotyping for the MTHFR and TS polymorphism may become a useful indicator in determining prognosis of epilepsy.