DNA methylation in childhood dental caries and hypomineralization

Silva Mj; Mohandas N; Craig Jm; Manton Dj; Saffery R; Southey Mc; Burgner Dp; Lucas J; Kilpatrick Nm; Hopper Jl; Scurrah Kj; Li S

doi:10.1016/j.jdent.2021.103913

DNA methylation in childhood dental caries and hypomineralization

J Dent. 2022 Feb:117:103913. doi: 10.1016/j.jdent.2021.103913. Epub 2021 Dec 5.

Authors

Silva Mj¹, Mohandas N², Craig Jm³, Manton Dj⁴, Saffery R², Southey Mc⁵, Burgner Dp⁶, Lucas J⁷, Kilpatrick Nm⁸, Hopper Jl⁹, Scurrah Kj¹⁰, Li S¹¹

Affiliations

¹ 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. Electronic address: mihiri.silva@mcri.edu.au.
² Epigenetics, Murdoch Children's Research Institute, Melbourne, Australia.
³ Epigenetics, Murdoch Children's Research Institute, Melbourne, Australia; Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Geelong, Australia.
⁴ Melbourne Dental School, University of Melbourne, Melbourne, Australia; Centrum voor Tandheelkunde en Mondzorgkunde, UMCG, University of Groningen, Groningen, The Netherlands.
⁵ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, Australia; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
⁶ Inflammatory Origins, Murdoch Children's Research Institute, Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Department of Paediatrics, Monash University, Clayton, Australia.
⁷ Melbourne Dental School, University of Melbourne, Melbourne, Australia.
⁸ Royal Children's Hospital, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; Facial Sciences, Murdoch Children's Research Institute, Melbourne, Australia.
⁹ Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
¹⁰ Facial Sciences, Murdoch Children's Research Institute, Melbourne, Australia; Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Australia.
¹¹ Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Melbourne, Australia; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, United Kingdom.

PMID: 34875274
DOI: 10.1016/j.jdent.2021.103913

Abstract

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.

Keywords: Dental enamel; Enamel hypomineralization; Epigenome; Longitudinal studies; Primary; Tooth; Twin studies.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Child
Cohort Studies
DNA Methylation / genetics
Dental Caries* / complications
Dental Caries* / genetics
Dental Enamel Hypoplasia* / genetics
Humans
Infant, Newborn
Prevalence

Grants and funding

R01 DE019665/DE/NIDCR NIH HHS/United States