Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and risk of hyperhomocysteinemia

D. Caccamo, S. Condello, G. Gorgone, G. Crisafulli, V. Belcastro, S. Gennaro, P. Striano, F. Pisani, R. Ientile

Research output: Contribution to journalArticlepeer-review


Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate reductase (MTHFR) enzyme activity, owing to genetic polymorphisms and/or inadequate folate intake. This study was aimed at investigating the prevalence of C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in 95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel electrophoresis screening revealed that the frequency of T677 polymorphic allele was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298 allele was significantly higher in patients (30.5% vs 19.4%, p <0.05). Significant differences between the two groups were also found for the frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p <0.01) and AC1298 (46.3% in cases vs 26.6% in controls, p <0.01). Other genotype frequencies did not show any statistically significant differences. Haplotype frequencies significantly differed between the two groups. The CT677/AC1298 diplotype was significantly more frequent in epileptic patients than in controls (32.6% vs 18.4%, p <0.05). Patients treated with enzyme-inducing antiepileptic drugs, having this diplotype and concomitant low folate concentration (i.e., <3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than normal values (27.1 ± 2.44 μmol/L, p <0.001). This increase, however, was lower than that observed in folate-deficient patients with diplotype TT677/AA1298 (41.3 ± 3.41 μmol/L, p <0.001). Indeed, these two diplotypes could be regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the CC677/AA1298 diplotype was significantly more frequent in controls (p <0.01), suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR polymorphisms should be examined when assessing genetic risk factors of hyperhomocysteinemia in epilepsy.

Original languageEnglish
Pages (from-to)117-126
Number of pages10
JournalNeuroMolecular Medicine
Issue number2-3
Publication statusPublished - Oct 2004


  • A1298C mutation
  • C677T mutation
  • Epilepsy
  • Hyperhomocysteinemia
  • Methylenetetrahydrofolate reductase
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology


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