Methylenetetrahydrofolate reductase gene is determinant of hyperhomocysteinemia in epileptic patients

ABSTRACT

Recent evidences mount that homocysteine level significantly increased in epileptic patients particularly those taking anticonvulsant drugs. Several previous studies revealed that a 677C T transition in the methylenetetrahydrofolate reductase [MTHFR] gene is related to Hyperhomocysteinemia and might increase risk of vascular occlusive pathology. However other publications negate this relationship. This study aimed to determine the prevalence of hyperhomocysteinemia, [MTHFR] gene 677C [right arrow] T mutations and whether this mutation is related to elevated homocysteine concentrations in epileptic patients and to determine the possible relationship between clinical data with elevated Hcy levels and genetic mutations. Twenty five epileptic patients [13 males, 12 females], their mean age is 15.08 +/- 13.7 divided into two groups according to medications Group 1 Newly diagnosed patients who did not receive medications yet. They were 16 patients, Group 2 Patients who received valproate. They were 9 patients. Fifteen healthy sex- and age-matched controls were recruited. After through neurological evaluation and EEG study, plasma total homocysteine [tHcy] level was determined by specific immunoassays [IMX, Abbott Laboratories]. MTHFR 677 C[right arrow]T mutation using a polymerase chain reaction [PCR] and restriction fragment length polymorphism analysis with HinfI digestion were investigated. The prevalence of hyperhomocysteinemia [>/= 11.4micromol/L, 90[th] percentile of control group] was significantly higher in the epileptic patients than in the controls [15 patients [60%] V one volunteer [6.6%] p<0.05]. The mean of homocysteine level was significantly higher in the epileptic patients than in the controls [10.23 +/- 5.9 V 5.35 +/- 1.64, p<0.05]. No significant correlation was found between clinical data [Age, sex, age of onset, seizure type, seizure frequency, duration and valproate medication] and homocysteine level. The homozygosity for the 677 C[right arrow]>T mutation of MTHFR was associated with elevated tHcy levels. The magnitude of hyperhomocysteinemia in MTHFR CT heterozygotes was more pronounced in epileptic patients than in controls [12.64 +/- 6.64 V 7.9 +/- 2.54 micromol/L, p<0.05]. Statistically significant differences is noticed between hetero mutant patients and patients with normal gene as regard mean homocysteine level [12.64 +/- 6.64 V 8.50 +/- 4.68 in p value <0.01]. The epileptic patients are at a higher risk of hyperhomocysteinemia. The C677T mutation in MTHFR gene contributes to hyperhomocysteinemia in epileptic patients. So measuring homocysteine in epileptic patients is recommended as early management of hyperhomocysteinemia help to avoid its devastating consequences