Metabolic and Genetic Risk Factors for Migraine in Children

Abstract

Migraine can induce ischaemic stroke, and is considered an independent risk factor for stroke in the young. To date, the nature of the link between migraine and stroke is essentially unknown. Forty-five children were studied. Homocysteine levels (fasting and post methionine load), vitamin B12 and plasma folate levels, factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C mutations were examined. Compared with controls, patients with migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/- 2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be related to migraine in the young, whereas the biochemical differences between migrainous patients and controls are an appealing topic for further investigation.

Are Methylenetetrahydrofolate Reductase (<i>MTHFR</i>) Gene Polymorphisms C677T and A1298C Associated with Higher Risk of Pediatric Migraine in Boys and Girls?

“…), but not in the Estonian population. A trend for migraine was reported in Italian patients who were 677TT and 1298CC homozygous carriers [24]. In the Croatian pediatric migraine population, no statistically significant association with migraine in carriers of 677CT polymorphism was found, but a trend toward an increased risk for migraine in patients who had homozygous variant 677TT was found [25].…”

The Headaches and Polymorphisms of the Methylenetetrahydrofolate Reductase

“…In a study of Bottini et al was analyzed the prevalence of homozygous variant of an Italian study population, it was identified a trend towards an increased incidence of migraine in subjects who carried the mutation [8]; another study examined a group of Croatian pediatric patients suffering from migraine, the 677TT genotype was associated with an higher risk of migraine [11]. No association was found in Spanish and Portuguese migraineurs with TT genotype [10,12,13] Lorenz et al analyzed MTHFR 677TT polymorphism in a group of Estonian pediatric migraineurs and did not detect a close link with migraine prevalence [14] MTHFR C677T variant differently occur in different countries, so it could be considered an ethnic-specific polymorphism [14].…”

“…A meta-analisys of 15 case control studies showed a close correlation between TT variant and Caucasians suffering from MA, in non-Caucasian population this genotype is associated with total migraine [11]. In a study of Bottini et al was analyzed the prevalence of homozygous variant of an Italian study population, it was identified a trend towards an increased incidence of migraine in subjects who carried the mutation [8]; another study examined a group of Croatian pediatric patients suffering from migraine, the 677TT genotype was associated with an higher risk of migraine [11]. No association was found in Spanish and Portuguese adult migraineurs [13,14].…”

“…The migraines are on a chapter of "The International Headache Society classification, 2013 version" [1] and were considered two different categories: migraine with aura (MA) and migraine without aura (MO). The MA has been related to Methylenetetrahydrofolate Reductase (MTHFR) gene mutation and high levels of Homocysteine (Hcy) [2][3][4][5][6][7][8]. Hcy is a product of methionine metabolism and is a sulfurcontaining amino acid [2][3][4].…”

“…C677T polymorphism is characterized by a substitution of an alanine with avaline at position 222; this substitution leads to a reduction on enzyme activity [6]. Subjects with the C677T variant present reduced capacity to remethylate homocysteine to methionine, these conditions increase homocysteine plasma levels [6,8]. In most of the genetic determination of C677T polymorphism studies carried out on whole blood samples using EDTA tubes and transferred in an upright position to local lab, where were stored at -20°C to freezer by the Real-Time Polymerase Chain Reaction (RT-PCR), and are considered the homozygous and heterozygous T alleles of variant [9].…”