Do Folate, Vitamins B6 and B12 Play a Role in the Pathogenesis of Migraine? The Role of Pharmacoepigenomics
Munvar Miya Shaik,
Huay Lin Tan,
Mohammad A Kamal,
Siew Hua Gan.
Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with
genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10-
methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma
homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of
complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate.
Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine
predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen
receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent
upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine.
Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and
oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the
occurrence of migraine.
Keywords: Migraine, flavoenzyme 5, 10-methylenetetrahydrofolate reductase, oestrogen receptor 1, Vitamins B, Estrogen,
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