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

John R. Shaffer; Jenna C. Carlson; Brooklyn O.C. Stanley; Eleanor Feingold; Margaret Cooper; Michael M. Vanyukov; Brion S. Maher; Rebecca L. Slayton; Marcia C. Willing; Steven E. Reis; Daniel W. McNeil; Richard J. Crout; Robert J. Weyant; Steven M. Levy; Alexandre R. Vieira; Mary L. Marazita

doi:10.1007/s00439-014-1504-7

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

John R. Shaffer, Jenna C. Carlson, Brooklyn O.C. Stanley, Eleanor Feingold, Margaret Cooper, Michael M. Vanyukov, Brion S. Maher, Rebecca L. Slayton, Marcia C. Willing, Steven E. Reis, Daniel W. McNeil, Richard J. Crout, Robert J. Weyant, Steven M. Levy, Alexandre R. Vieira, Mary L. Marazita

Bloomberg School of Public Health

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

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 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.

Original language	English (US)
Pages (from-to)	159-167
Number of pages	9
Journal	Human genetics
Volume	134
Issue number	2
DOIs	https://doi.org/10.1007/s00439-014-1504-7
State	Published - Jan 13 2015

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1007/s00439-014-1504-7

Cite this

Shaffer, J. R., Carlson, J. C., Stanley, B. O. C., Feingold, E., Cooper, M., Vanyukov, M. M., Maher, B. S., Slayton, R. L., Willing, M. C., Reis, S. E., McNeil, D. W., Crout, R. J., Weyant, R. J., Levy, S. M., Vieira, A. R., & Marazita, M. L. (2015). Effects of enamel matrix genes on dental caries are moderated by fluoride exposures. Human genetics, 134(2), 159-167. https://doi.org/10.1007/s00439-014-1504-7

Shaffer, JR, Carlson, JC, Stanley, BOC, Feingold, E, Cooper, M, Vanyukov, MM, Maher, BS, Slayton, RL, Willing, MC, Reis, SE, McNeil, DW, Crout, RJ, Weyant, RJ, Levy, SM, Vieira, AR & Marazita, ML 2015, 'Effects of enamel matrix genes on dental caries are moderated by fluoride exposures', Human genetics, vol. 134, no. 2, pp. 159-167. https://doi.org/10.1007/s00439-014-1504-7

@article{cff46ea340904add8ab74ea08ff51092,

title = "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 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.",

author = "Shaffer, {John R.} and Carlson, {Jenna C.} and Stanley, {Brooklyn O.C.} and Eleanor Feingold and Margaret Cooper and Vanyukov, {Michael M.} and Maher, {Brion S.} and Slayton, {Rebecca L.} and Willing, {Marcia C.} and Reis, {Steven E.} and McNeil, {Daniel W.} and Crout, {Richard J.} and Weyant, {Robert J.} and Levy, {Steven M.} and Vieira, {Alexandre R.} and Marazita, {Mary L.}",

note = "Publisher Copyright: {\textcopyright} 2014, Springer-Verlag Berlin Heidelberg.",

year = "2015",

month = jan,

day = "13",

doi = "10.1007/s00439-014-1504-7",

language = "English (US)",

volume = "134",

pages = "159--167",

journal = "Human genetics",

issn = "0340-6717",

publisher = "Springer Verlag",

number = "2",

}

TY - JOUR

T1 - Effects of enamel matrix genes on dental caries are moderated by fluoride exposures

AU - Shaffer, John R.

AU - Carlson, Jenna C.

AU - Stanley, Brooklyn O.C.

AU - Feingold, Eleanor

AU - Cooper, Margaret

AU - Vanyukov, Michael M.

AU - Maher, Brion S.

AU - Slayton, Rebecca L.

AU - Willing, Marcia C.

AU - Reis, Steven E.

AU - McNeil, Daniel W.

AU - Crout, Richard J.

AU - Weyant, Robert J.

AU - Levy, Steven M.

AU - Vieira, Alexandre R.

AU - Marazita, Mary L.

PY - 2015/1/13

Y1 - 2015/1/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84925506653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925506653&partnerID=8YFLogxK

U2 - 10.1007/s00439-014-1504-7

DO - 10.1007/s00439-014-1504-7

M3 - Article

C2 - 25373699

AN - SCOPUS:84925506653

SN - 0340-6717

VL - 134

SP - 159

EP - 167

JO - Human genetics

JF - Human genetics

IS - 2

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this