Methylenetetrahydrofolate reductase gene polymorphism and clinical importance in epilepsy patients using valproic acid, carbamazepine and levetiracetam

Abstract

Background: We aim to determine the relationships among vitamin B-12, folic acid, homocysteine (Hcy), and methylenetetrahydrofolatereductase (MTHFR) C677T polymorphism, as well as the clinical importance of these relationships, in patients using valproic acid (VPA), carbamazepine (CBZ), and levetiracetam (LEV) as monotherapy and polytherapy. Methods: We enrolled 37 patients on VPA, 30 on CBZ, 31 on LEV, 30 on multidrug therapy, and 60 control subjects. We compared the levels of vitamin B-12, folic acid, Hcy and polymorphism. Results: Vitamin B-12 was low in patients on CBZ (p = 0.02) and in combined CBZ and VPA (p = 0.02). B-12 was low in combined CBZ and VPA (p = 0.05). In patients without polymorphism, Hcy was high on VPA (p = 0.02), and folic acid was the low on CBZ (0.005). In patients with polymorphism, vitamin B-12 was low on CBZ (p = 0.02), and folic acid was low on VPA (p = 0.04). Vitamin B-12 was low in combined CBZ and VPA (p = 0.05). Conclusions: Vitamin B-12 therapy is necessary on CBZ and on combined CBZ and VPA. VPA should not be used in the presence of other thrombophilic risk factors because of hyperhomocysteinemia. Polytherapy does not increase hyperhomocysteinemia risk in comparison to monotherapy. Vitamin B-12, folic acid, Hcy do not effect on seizure frequency.