Effects of enamel matrix genes on dental caries are moderated by fluoride exposures

Abstract

Dental caries (tooth decay) is the most common chronic disease, worldwide, affecting most children and adults. Though dental caries is highly heritable, few caries-related genes have been discovered. We investigated whether 18 genetic variants in the group of nonamelogenin enamel matrix genes (AMBN, ENAM, TUFT1, and TFIP11) were associated with dental caries experience in 13 age- and race-stratified samples from six parent studies (N=3,600). Linear regression was used to model genetic associations and test gene-byfluoride interaction effects for two sources of fluoride: daily tooth brushing and home water fluoride concentration. Meta-analysis was used to combine results across five child and eight adult samples. We observed the statistically significant association of rs2337359 upstream of TUFT1 with dental caries experience via meta-analysis across adult samples (p<0.002) and the suggestive association for multiple variants in TFIP11 across child samples (p<0.05). Moreover, we discovered two genetic variants (rs2337359 upstream of TUFT1 and missense rs7439186 in AMBN) involved in gene-by-fluoride interactions. For each interaction, participants with the risk allele/genotype exhibited greater dental caries experience only if they were not exposed to the source of fluoride. Altogether, these results confirm that variation in enamel matrix genes contributes to individual differences in dental caries liability, and demonstrate that the effects of these genes may be moderated by protective fluoride exposures. In short, genes may exert greater influence on dental caries in unprotected environments, or equivalently, the protective effects of fluoride may obviate the effects of genetic risk alleles.

Single Nucleotide Polymorphism in the Aetiology of Caries: Systematic Literature Review

“…Although they all coexist in caries aetiology, the research studies usually focus on one of these components. Only a small number of studies was dedicated to analysing the interactions of genetic and environmental factors [Wang et al, 2012b;Chaussain et al, 2014;Abbasoğlu et al, 2015;Shaffer et al, 2015;Yildiz et al, 2016]. Future studies should associate some further information, such as metagenomics, protein-protein interaction, and gene expression, as they may be linked with caries Nibali et al, 2016].…”

“…Authors of some studies included in the review observed the SNP phenomenon in genes involved in amelogenesis [Slayton et al, 2005;Deeley et al, 2008;Patir et al, 2008Kang et al, 2011;Olszowski et al, 2012;Shimizu et al, 2012;Tannure et al, 2012a, b;Wang et al, 2012b;Gasse et al, 2013;Chaussain et al, 2014;Duverger et al 2014;Abbasoğlu et al, 2015;Anjomshoaa et al, 2015;Shaffer et al, 2015;Yildiz et al, 2016]. Amelogenesis is a genetically controlled process of enamel development.…”

Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries

“…Home water source fluoride concentration was dichotomized as greater than 0.7 ppm versus less than 0.7 ppm, representing sufficient and insufficient fluoride concentrations, respectively. Tooth brushing frequency was dichotomized as daily or more frequent tooth brushing versus less frequent than daily brushing, which reflects the consensus in the literature that at least daily brushing is needed 33 , and is consistent with the dichotomization used in previous studies 9, 27, 34 .…”

“…In light of recent results documenting gene-by-fluoride exposure interaction effects on dental caries 26, 27 , we also tested for interaction effects with the two fluoride exposures in the samples of sufficient size for which fluoride exposure data were available (i.e., COHRA1 white adults and COHRA1 white children). These fluoride exposures were dichotomized measures of home water source fluoride (<0.7 ppm vs. ≥0.7 ppm) and tooth brushing frequency (once or more per daily vs. less often than once per day).…”

“…Furthermore, because previous studies have identified statistical interaction effects on caries between other SCPP genes and fluoride exposures 26, 27 , we also explored whether fluoride may mediate the association of SIBLINGs variants with caries.…”