Shaik Munvar Miya, Tan Huay Lin, Kamal Mohammad A, Gan Siew Hua
Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia.
CNS Neurol Disord Drug Targets. 2014;13(5):828-35. doi: 10.2174/18715273113129990112.
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.
偏头痛是一种神经血管疾病，传统上认为其病因是多因素的，遗传因素和环境相互作用被视为主要影响因素。诸如黄素酶5、10-亚甲基四氢叶酸还原酶（MTHFR）等基因，尤其是C677T变体，与血浆同型半胱氨酸水平升高有关。同型半胱氨酸水平的升高会导致一系列代谢紊乱，并增加包括偏头痛在内的复杂疾病的风险。同型半胱氨酸的催化需要维生素B6、B12和叶酸的存在。这些辅助因子维生素的缺乏会导致低甲基化，从而引发偏头痛。由于偏头痛主要影响女性，因此推测由雌激素受体1多态性控制的雌激素水平波动很重要。另一个重要因素是同型半胱氨酸，其产生依赖于MTHFR和B族维生素。基因表达通过表观遗传机制进行调节，这涉及蛋氨酸。此外，叶酸在DNA合成中起主要作用。我们提出，维生素B的摄入，加上MTHFR和雌激素受体1多态性，会导致不同的DNA甲基化和基因表达，这可能导致偏头痛的发生。
