A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants.
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 HinfI digestion in 103 patients with epilepsy and 103 normal controls. The prevalence of hyperhomocysteinemia (> or = 11.4 micromol/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 micromol/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.
Yoo
J H
JH
Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hong
S B
SB
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation
D000927:Anticonvulsants; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)