Inflammatory Origins, Murdoch Children's Research Institute, Melbourne, Australia; Melbourne Dental School, University of Melbourne, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Epigenetics, Murdoch Children's Research Institute, Melbourne, Australia.
J Dent. 2022 Feb;117:103913. doi: 10.1016/j.jdent.2021.103913. Epub 2021 Dec 5.
Epigenetic modulation of gene expression may be important in dental conditions, including dental caries and enamel hypomineralisation. The aims of this study were to assess associations between DNA methylation in cord blood leucocytes at birth, and caries experience and enamel hypomineralisation at six years of age.
The study sample was from a birth cohort study of twins. Dental examinations at six years identified the presence/absence of (i) 'any caries' (untreated and treated caries), (ii) 'advanced caries' (untreated, advanced caries and/or past treatment) and (iii) hypomineralised second primary molars (HSPM). Genome-wide analysis of DNA methylation was performed on cord blood of 27 twin pairs (14 dizygotic and 13 monozygotic) using the Illumina Infinium MethylationEPIC BeadChip array. Differentially methylated CpGs (DMCpGs) and regions (DMRs) associated with each dental outcome were investigated, while accounting for the relatedness of twins. Results with a false discovery rate <0.05 were treated as statistically significant.
19 children had 'any caries', 15 had 'advanced' caries, and 18 had HSPM. No DMCpGs were associated with 'any caries', 16 and 19 DMCpGs were associated with 'advanced caries' and HSPM, respectively. DMRs were identified in association with all three outcomes. Genes implicated by these analyses included PBX1, ACAT2, LTBP3 and DDR1 which have been linked with dental tissue development in genetic studies.
This exploratory study identified differential methylation in several genes at birth associated with dental caries and HSPM at six years. Further research may provide valuable insights into aetiology of dental disease and/or reveal novel molecular-based approaches for early risk stratification.
Epigenetic differences at birth are likely to be associated with dental health at six years and may be valuable biomarkers of early influences on dental health.
基因表达的表观遗传调控可能在包括龋齿和釉质发育不全在内的口腔状况中具有重要意义。本研究旨在评估出生时脐带血白细胞中的 DNA 甲基化与 6 岁时龋齿发生和釉质发育不全之间的相关性。
本研究样本来自双胞胎的出生队列研究。6 岁时的口腔检查确定了（i）“任何龋齿”（未经治疗和治疗的龋齿）、（ii）“进展性龋齿”（未经治疗、进展性龋齿和/或既往治疗）和（iii）第二恒磨牙矿化不全（HSPM）的存在/缺失。使用 Illumina Infinium MethylationEPIC BeadChip 芯片对 27 对双胞胎（14 对异卵双胞胎和 13 对同卵双胞胎）的脐带血进行全基因组 DNA 甲基化分析。在考虑双胞胎相关性的情况下，研究了与每个口腔结局相关的差异甲基化 CpG（DMCpG）和区域（DMR）。具有错误发现率 <0.05 的结果被视为具有统计学意义。
19 名儿童患有“任何龋齿”，15 名儿童患有“进展性”龋齿，18 名儿童患有 HSPM。没有 DMCpG 与“任何龋齿”相关，16 和 19 个 DMCpG 分别与“进展性龋齿”和 HSPM 相关。还确定了与所有三种结局相关的 DMR。通过这些分析提示的基因包括 PBX1、ACAT2、LTBP3 和 DDR1，它们在遗传研究中与牙组织发育有关。
本探索性研究在出生时发现了与 6 岁时龋齿和 HSPM 相关的几个基因的差异甲基化。进一步的研究可能为口腔疾病的病因学提供有价值的见解，或揭示用于早期风险分层的新的基于分子的方法。
出生时的表观遗传差异可能与 6 岁时的口腔健康相关，并且可能是口腔健康早期影响的有价值的生物标志物。
