环境因素诱导的DNA甲基化修饰在唇腭裂发病中的作用研究进展

Research progress on the role of environmentally induced DNA methylation in congenital cleft lip and/or palate

先天性唇腭裂(cleft lip with/without palate,CL/P)作为常见的颌面部发育畸形,其病因目前认为主要是遗传因素和环境因素共同作用的结果。研究发现,环境因素诱发的表观遗传学变化可能是胎儿先天畸形发生的关键因素,而DNA甲基化作为重要的表观遗传修饰之一,在众多领域已有广泛而深入的研究,但其作为联系个体与环境的纽带,在唇腭裂中的研究报道有限。现有研究表明,DNA甲基化与唇腭裂的发生密切相关,叶酸缺乏、吸烟、污染物暴露等不良环境因素的刺激可诱导DNA甲基化状态发生改变,从而影响唇腭发育的基因表达,导致畸形的发生。

Congenital cleft lip and/or palate(CL/P)is a common malformation of maxillofacial development.At pres⁃ent,it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmen⁃tal factors.Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congen⁃ital malformations.As one of the important epigenetic modifications,DNA methylation has been widely and deeply stud⁃ied in many fields,but as a link between the individual and the environment,its application in CL/P is limited.Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate.Stimulation of fo⁃late deficiency,smoking,pollutant exposure and other environmental factors can induce changes in the state of DNA methylation,thus affecting gene expression in the development of lip and palate and leading to the occurrence of defor⁃mities.