摘要目的:初步探讨甲基化在非综合征型口面裂（NSOC）发病机制中的表观遗传调控作用。方法:利用来自一大规模中国汉族非综合征型唇腭裂（NSCLP）患者与健康对照的全基因组关联研究数据，进行单核苷酸多态性（SNP）位点及与甲基化相关的基因的关联分析。结果:NSOC与DNA甲基化基因TET1和组蛋白甲基化基因NSD1之间存在显著关联。具体而言，rs3733875的次要等位基因G显著增加了NSCLP的风险（ P=1.18×10 -14， OR=1.292），rs10998379的次要等位基因C则提升了非综合征型腭裂的风险（ P=7.29×10 -5， OR=1.268），而rs4558056的次要等位基因T则是NSCL/P的保护因素（ P=1.17×10 -4， OR=0.792）。 结论:本研究发现DNA甲基化基因TET1与组蛋白甲基化基因NSD1与NSOC相关。NSOC的发病涉及遗传、环境及表观遗传等多层次因素的相互影响，而甲基化修饰更是其中不可忽视的重要环节。

abstractsObjective:To preliminarily investigate the role of methylation in the epigenetic regulation of the pathogenesis of non-syndromic orofacial clefts (NSOC), and to address the gaps in previous explorations of susceptibility genes associated with NSOC.Methods:We conducted an association analysis of single nucleotide polymorphisms (SNPs) and genes related to methylation using data from a large-scale genome-wide association study involving Han Chinese patients with non-syndromic orofacial clefts and healthy controls.Results:A significant association was found between NSOC and the DNA methylation gene TET1, as well as the histone methylation gene NSD1. Specifically, the minor allele G of rs3733875 significantly increased the risk of non-syndromic cleft lip with or without palate (NSCLP) ( P=1.18×10 -4, OR=1.292), while the minor allele C of rs10998379 elevated the risk of non-syndromic cleft palate only (NSCPO) ( P=7.29×10 -5, OR=1.268); conversely, the minor allele T of rs4558056 was identified as a protective factor for NSCL/P ( P=1.17×10 -4, OR=0.792). Conclusions:This study revealed that the DNA methylation gene TET1 and the histone methylation gene NSD1 are associated with NSOC. The pathogenesis of NSOC involves interactions among multiple factors, including genetic, environmental, and epigenetic determinants, among which methylation modifications represent a crucial component.