Epigenetics of Dental Development

Objectives: Developmental anomalies of the dentition have clinical implications. There is growing evidence that these conditions share common genetic influences.  Our group has been exploring this using Australian twin cohorts. Phenotypic discordance in monozygous (MZ) co-twins traditionally indicates the influence of the environment.  Evidence has been accumulating that epigenetic modifications may also have a role in phenotypic discordance. DNA methylation, one of three key epigenetic processes, is fundamental for embryological development and has been implicated in disease. The aim of this study was to determine whether differential DNA methylation is associated with differential expression of dental anomalies.

Methods: The population was sourced from a cohort of Australian twins with available DNA. Phenotypic records included tooth charts of permanent dentition, tooth dimensions and tooth volume.  The control group comprised 10 MZ pairs with no agenesis/supernumeraries.  The first test group comprised 14 MZ pairs discordant for agenesis.  The second test group comprised 6 MZ pairs discordant for supernumerary teeth.  Groups were ascertained across a range of tooth sizes.  Equal numbers of male and female pairs were selected.  DNA samples were subjected to genome-wide methylation analysis using the Illumina450 microarray, interrogating ~485,000 CpG sites.  Following routine quality control and data cleaning, we plan to analyse genome-wide and site-specific associations.

Results: Despite modest degradation, all samples yielded methylation data.  All except one control sample yielded >425,000 CpG sites.  Preliminary analysis of intra-pair correlations for average beta indicated discordance between many MZ twins.  There was some evidence that the discordance was greater for twins discordant for dental anomalies.

Conclusions: This is the first study to suggest that epigenetic factors may play a role in early dental development. Our preliminary analysis suggests that, genome-wide, there may be an influence of methylation status on tooth embryogenesis.  More sophisticated analyses are required for a definitive answer.