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

Background: We aim to determine the relationships among vitamin B12, 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 B12, folic acid, Hcy and polymorphism. Results: Vitamin B12 was low in patients on CBZ (p=0.02) and in combined CBZ and VPA (p=0.02). B12 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 B12 was low on CBZ (p=0.02), and folic acid was low on VPA (p=0.04). Vitamin B12 was low in combined CBZ and VPA (p=0.05). Conclusions: Vitamin B12 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 B12, folic acid, Hcy do not effect on seizure frequency.