Effects of enamel matrix genes on dental caries are moderated by fluoride exposures.
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 non-amelogenin 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-by-fluoride 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.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 De Soto Street, A300 Crabtree Hall, Pittsburgh, PA, 15261, USA, jrs51@pitt.edu.
John R
JR
Shaffer
Jenna C
JC
Carlson
Brooklyn O C
BO
Stanley
Eleanor
E
Feingold
Margaret
M
Cooper
Michael M
MM
Vanyukov
Brion S
BS
Maher
Rebecca L
RL
Slayton
Marcia C
MC
Willing
Steven E
SE
Reis
Daniel W
DW
McNeil
Richard J
RJ
Crout
Robert J
RJ
Weyant
Steven M
SM
Levy
Alexandre R
AR
Vieira
Mary L
ML
Marazita
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003731:Dental Caries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003743:Dental Enamel; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005459:Fluorides; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020125:Mutation, Missense
D005459:Fluorides