Original article| Volume 24, ISSUE 4, P223-226, June 2002

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The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants


      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.


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        • Hankey G.J
        • Eikelboom J.W
        Homocysteine and vascular disease.
        Lancet. 1999; 354: 407-413
        • Ono H
        • Sakamoto A
        • Eguchi T
        • Sakura N
        • Noumura S
        • Fujita N
        • et al.
        Plasma total homocysteine concentrations in epileptic patients taking anticonvulsants.
        Metabolism. 1997; 46: 959-962
        • James G.K
        • Jones M.W
        • Pudek M.R
        Homocyst(e)ine levels in patients on phenytoin therapy.
        Clin Chem. 1997; 30: 647-649
        • Schwaninger M
        • Ringleb P
        • Winter R
        • Kohl B
        • Fiehn W
        • Rieser P.A
        • et al.
        Elevated plasma concentrations of homocysteine in antiepileptic drug treatment.
        Epilepsia. 1999; 40: 345-350
        • Frosst P
        • Blom H.J
        • Milos R
        • Goyette P
        • Sheppard C.A
        • Matthews R.G
        • et al.
        A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase.
        Nat Genet. 1995; 10: 111-113
        • Rozen R
        Molecular genetics of methylenetetrahydrofolate reductase deficiency.
        J Inherit Metab Dis. 1996; 19: 589-594
        • Yoo J.H
        • Hong S.B
        A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants.
        Metabolism. 1999; 48: 1047-1051
        • Blom H.J
        Mutated 5,10-methylenetetrahydrofolate reductase and moderate hyperhomocysteinenaemia.
        Eur J Pediatr. 1998; 157: S131-S134
        • Boushey C.J
        • Beresford S.A
        • Omenn G.S
        • Motulsky A.G
        A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intake.
        J Am Med Assoc. 1995; 274: 1049-1057
        • Marangos P.J
        • Loftus T
        • Wiesner J
        • Lowe T
        • Rossu E
        • Browne C.E
        • et al.
        Adenosinergic modulation of homocysteine-induced seizures in mice.
        Epilepsia. 1990; 31: 239-246
        • Mudd S.H
        • Levy H.L
        • Skovby F
        Disorders of transsulfuration.
        in: Charles R.S Arthur L.B William S.S David V The metabolic and molecular bases of inherited disease. 7th ed. McGraw-Hill, New York, NY1995: 1279-1327
        • Mudd S.H
        • Skovby F
        • Levy H.L
        • Pettigrew F.D
        • Wlekeu B
        • Pyritz R.E
        • et al.
        The natural history of homocystinuria due to cystathionine β-synthase deficiency.
        Am J Hum Genet. 1985; 37: 1-31