Orthognathic surgery induces genomewide changes longitudinally in DNA methylation in saliva: XXXX

OBJECTIVE: Orthognathic surgery dramatically changes morphology of the maxillofacial deformity and improves the malocclusion morphologically and functionally. We investigated the influence of orthognathic surgery on genomewide DNA methylation in saliva. METHODS: Saliva was obtained from nine patients undergoing orthognathic surgery and two healthy reference individuals before and 3 months after orthognathic surgery. Genomewide DNA methylation profiling of saliva (341,482 CpG dinucleotides) was conducted using Infinium HumanMethylation450 BeadChips. RESULTS: Comparison between pre- and postsurgery saliva samples revealed significant changes in DNA methylation patterns at 2,381 CpG sites (p < 0.01) with suggestive significance. The differentially methylated probe sets were significantly associated with the cancer pathway (p = 2.8 × 10-7 ; a false discovery rate q-value = 3.7 × 10-4 ) and PI3K-Akt signalling pathway (p = 2.4 × 10-5 ; a false discovery rate q-value = 3.1 × 10-2 ). CONCLUSION: Pathway enrichment analysis of genes with suggestive significance demonstrated that altered DNA methylation in saliva of patients undergoing orthognathic surgery, possibly as a response to surgical stress or bone injury. Further studies with a large sample size and long-term observation are needed to validate the phenomena identified in this study.