title: The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants.
abstract: Hyperhomocysteinemia, a possible risk factor for vascular disease can result from folate deficiency due to anticonvulsant therapy. A reaction catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR) supplies 5-methyltetrahydrofolate, needed to remethylate homocysteine to methionine. MTHFR gene mutation (C677T) also can lead to hyperhomocysteinemia. We examined interaction between anticonvulsant therapy, C677T homozygosity, serum folate concentration, and plasma total homocysteine (tHcy) concentration in 81 epileptic patients. Patients receiving monotherapy showed no difference in occurrence of hyperhomocysteinemia (tHcy>90th percentile for controls) between homozygotes for C677T and heterozygotes or patients with no mutant MTHFR. No monotherapy patient was folate deficient (<3 ng/ml). Among patients receiving multidrug therapy, hyperhomocysteinemia in homozygotes for C677T occured significantly more often than in heterozygotes or patients with no mutant enzyme (88.9 vs. 21.1%). The same was true for folate deficiency (44.4 vs. 0%). The C677T mutation is closely related to hyperhomocysteinemia and folate deficiency in epileptic patients taking multiple anticonvulsants.
authors.affiliation: Department of Pediatrics, Hiroshima University School of Medicine, Kasumi 1-2-3, Minami-ku, Japan. onohi@hiroshima-u.ac.jp
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ono
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizoguchi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakura
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000201:enzymology / Q000235:genetics; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D007223:Infant; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation
chemical_list: D000927:Anticonvulsants; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)