叶酸缺乏引起的甲基化异常在神经管缺陷中的重要性

Importance of abnormal methylation caused by folic acid deficiency in neural tube defects

神经管畸形(neural tube defects,NTDs)是一类由于神经管闭合障碍引起的出生缺陷,临床表型主要为先天性无脑畸形和脊柱裂。NTDs是一种多病因、多层次、多机制的复杂性疾病,遗传和环境因素在其发生过程中均发挥了重要作用,但其发病机制仍然不清楚。饮食中补充叶酸已被证明对预防神经管缺陷是非常有益的,叶酸缺乏也是NTDs的主要发病原因,其引起的叶酸代谢紊乱及S-腺苷甲硫氨酸下降,导致甲基供体减少,进而引起甲基化修饰紊乱。甲基化修饰是最重要的表观遗传修饰之一,其对大脑神经发育至关重要。

Neural tube defects(NTDs)are a kind of birth defects caused by neural tube closure disorders.The clinical phenotype is mainly congenital anencephaly and spina bifida.NTDs are complex disease caused by multiple etiology,multiple levels,and multiple mechanisms.At present,pathogenesis of NTDs is considered to be associated with both genetic and environmental factors.The underlying genetic risks and mechanisms of NTDs still need to be further investigated.Folic acid supplementation in the diet has been shown to be very beneficial in preventing neural tube defects.Folic acid deficiency is also the main pathogenesis of NTDs,results in disturbances on folic acid metabolism and decreased S-adenosylmethionine,leading to reduced methyl donors,and causes methylation modification disorders.Methylation modification is one of the most important epigenetic modifications,which is crucial for brain neurodevelopment.