The polymorphism of enzyme MTHFR in children suffering from migraine ad epilepsy

The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased levels of circulating homocysteine and is a mild risk factor for vascular disease. Mild Hcy elevation (>15 mmol L−1) in the adult population is associated with increased risk of myocardial infarction, stroke, peripheral arterial disease and venous thrombosis.[1,2,3] The MTHFR 677CT mutation is frequent in Caucasians; MTHFR mutant allele occurs commonly in 5% to 15% of the population, and the heterozygosis is over 40%. The C677T polymorphism of the MTHFR gene has been associated with different diseases such as stroke, coronary artery disease, bipolar disorder, schizophrenia and depression. Homozygosis for MTHFR 677 CT mutations is more frequent in epileptic patients compared with healthy controls (23% vs. 12%) and heterozygosis is about 52%. Lipton[1] showed that Hcy may have excitotoxicity to neurons as an agonist of the glutamate binding site of the N-methyl-Daspartate (NMDA) receptors. Migraine, with and without aura (MA and MO), is a prevalent and complex neurovascular disorder that may also be affected by genetically influenced hyperhomocysteinaemia Aim of this study is the evaluation of incidence of mutation of enzyme MTHFR in the children suffering from two disease, epilepsy and migraine as in comorbility, as without comorbility. MATERIALS AND METHODS 32 patients suffering from headache observed during 3 months and 34 children affected by epilepsy observed during the same time represent the sample of this study. At the first observation in day hospital are determined the homocisteinaemia levels and mutation C677 of enzyme MTHFR. In the sample is studied MR brain and EEG. In the familial history is considered the headache, the epilepsy, the stroke and cardiovascular disease. The homocisteinaemia is evaluated by immunological fluorescent method (FPIA) The mutation of enzyme C677 is studied by technique of qualititative Real-Time PCR. RESULTS 27 patients suffering from generalized epilepsy, 7 from partial epilepsy. In the 18%of these patients there is C677 enzyme mutation and 7% show homozygous condition. Among 32 children suffering from headache, 17 have TTH, 9 MO, and 6 MA. 50% show MTHFR mutation. The allele is present in the 83% of MO and in 87% of MA and homozygosis condition is present in 22% of children. The values of homocisteinaemia are higher in the homozygous than heterozygous patients (9.48 µmol/L vs. 8.3 µmol/L) and this condition is more evident in the migraines than epileptic patients. In the 50% of the sample with C677 mutation there are MR lesions as cerebrovascular disease. 1 child shows the results of ischemic event in the foetal life. We underline the history of 2 patient’s hemiplegic suffering, one from migraine, one from epilepsy. DISCUSSION Kowa et al. [1] originally reported a positive association between the MTHFR C677T variant and migraine in a Japanese case control cohort. These researchers indicated an increased risk of migraine in Japanese individuals possessing the homozygous T/T genotype. Stratified analyses specifically showed that the T/T genotype was significantly over-represented in these Japanese patients with MA compared to non-migraine controls (40% vs. 9.6%), producing an OR of ~6. These positive findings were reinforced by another recent migraine case-control study conducted in a Turkish population. These researchers reported that the MTHFR C677T is associated with migraine and also indicated that the T/T genotype specifically increased risk of MA (OR ~10). It is important to note that the frequency of the MTHFR 677T allele, and indeed migraine prevalence, is known to vary substantially among different ethnic populations. Thus, this study supports the findings of other authors and shows the hypothetical role of this genetically aspects in the comorbility migraine - epilepsy. 1. BMC Medicine 2 (2004):3 2. Cephalalgia 28 (2008): 376-382 3 Eur J Radiol 2009 feb 10