Elsevier

Metabolism

Volume 48, Issue 8, August 1999, Pages 1047-1051
Metabolism

A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants

https://doi.org/10.1016/S0026-0495(99)90204-4Get rights and content

Abstract

Hyperhomocysteinemia is a condition caused by both genetic and nongenetic factors. To determine whether a common methylenetetrahydrofolate reductase (MTHFR) variant is related to elevated homocysteine concentrations in epileptic patients receiving anticonvulsants, we investigated the plasma total homocysteine (tHcy) level, folate level, and MTHFR 677 C → T mutation using a polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis with Hinfl digestion in 103 patients with epilepsy and 103 normal controls. The prevalence of hyperhomocysteinemia (≥ 11.4 μmol/L, 90th percentile of control group) was higher in patients than in controls (25% v 10.0%, P = .007). The homozygosity for the 677 C → T mutation of MTHFR was associated with elevated tHcy and low folate levels. The magnitude of hyperhomocysteinemia in MTHFR TT homozygotes was more pronounced in epileptic patients than in controls (18.2 ± 1.6 v 9.1 ± 1.2 μmol/L, P = .04). In epileptic patients, hyperhomocysteinemia was more frequent in MTHFR TT genotypes versus CT or CC genotypes (58% v 17% and 16%, P < .001). Multiple logistic regression analysis showed that MTHFR TT genotype was an independent predictor of hyperhomocysteinemia in epileptic patients receiving anticonvulsants (phenytoin and carbamazepine but not valproic acid), suggesting that gene-drug interactions induce hyperhomocysteinemia. These findings indicate that epileptic patients receiving anticonvulsants may have a higher folate requirement to maintain a normal tHcy level, especially homozygotes for MTHFR 677 C → T mutation.

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    Supported by the research fund of Samsung Biomedical Research Institute (C-98-029) and Samsung Medical Center.

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