The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for migraine

Abstract

Increased homocysteine levels are associated with various pathological conditions in humans, including stroke and cardiovascular disorders. Homocysteine acts as an excitatory amino acid in vivo and may influence the threshold of migraine headache. Frosst et al. [1995] reported an association between the homozygous C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and serum homocysteine levels. This study was designed to determine the prevalence of the MTHFR mutation in Japanese patients with migraine and tension-type headache (TH). Seventy-four patients with migraine headaches (22 with aura and 52 without aura), 47 with THs, and 261 normal controls were recruited. Genotyping of MTHFR C677T polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism. We detected that the incidence of the homozygous transition (T/T) in migraine sufferers (20.3%) was significantly higher than that in controls (9.6%). Moreover, the frequency of the T/T genotype in individuals with migraine headaches with aura was remarkably high (40.9%). The MTHFR T allele was more frequent in the migraine group than in the control group. Our results support the conclusion that the MTHFR gene, causing mild hyperhomocysteinemia may be a genetic risk factor for migraine. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:762-764, 2000.

The Headaches and Polymorphisms of the Methylenetetrahydrofolate Reductase

“…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].…”

“…MTHFR is an enzyme responsible for the conversion of Hcy to methionine and it catalyzes the reduction of 5,10-methylenetetrahydrofolate (CH2-THF) to 5-methylenetetrahydrofolate [4]. If Hcy is not properly metabolized, its high levels could be associated with vascular damage and endothelial remodelling, this condition could be responsible of a reduction in blood oxygenation in brain circulation close to onset and maintenance of migraine attacks [5,6]. The polymorphism most frequently identified is C677T and it is related not only to migraine, but also to other neurological/ psychiatric and organic symptoms as neural tube defects, cerebrovascular and cardiovascular disease, hypertension, glaucoma.…”

“…Among neurological and psychiatric disorders that are associated with migraine, depression, anxiety disorders, epilepsy and sleep disorders are reported. More recently, an association with cardiovascular disease has been highlighted, particularly with ischemic stroke [4][5][6][7]. 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].…”

“…More recently, an association with cardiovascular disease has been highlighted, particularly with ischemic stroke [4][5][6][7]. 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].…”

“…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].…”