DNA methylation in childhood dental caries and hypomineralization.

Objectives: 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.

Method: 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.

Results: 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.

Conclusion: 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.

Clinical Significance: 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.