[Association analysis of methylation-related genes TET1 and NSD1 with non-syndromic orofacial clefts]

Objective: 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.