Biomaterial Database

Effects of enamel matrix genes on dental caries are moderated by fluoride exposures. 2015

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

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.

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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D002648	Child	A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.	Children
D002675	Child, Preschool	A child between the ages of 2 and 5.	Children, Preschool,Preschool Child,Preschool Children
D003731	Dental Caries	Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp.	Caries, Dental,Carious Lesions,Dental Cavities,Dental Cavity,Dental Decay,Dental White Spots,Carious Dentin,Decay, Dental,Dental White Spot,White Spot, Dental,White Spots, Dental,Carious Dentins,Carious Lesion,Cavities, Dental,Cavity, Dental,Dentin, Carious,Dentins, Carious,Lesion, Carious,Lesions, Carious,Spot, Dental White,Spots, Dental White
D003743	Dental Enamel	A hard thin translucent layer of calcified substance which envelops and protects the dentin of the crown of the tooth. It is the hardest substance in the body and is almost entirely composed of calcium salts. Under the microscope, it is composed of thin rods (enamel prisms) held together by cementing substance, and surrounded by an enamel sheath. (From Jablonski, Dictionary of Dentistry, 1992, p286)	Enamel,Enamel Cuticle,Dental Enamels,Enamel, Dental,Enamels, Dental,Cuticle, Enamel,Cuticles, Enamel,Enamel Cuticles,Enamels
D005109	Extracellular Matrix	A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.	Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D005260	Female		Females
D005459	Fluorides	Inorganic salts of hydrofluoric acid, HF, in which the fluorine atom is in the -1 oxidation state. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Sodium and stannous salts are commonly used in dentifrices.	Fluoride
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes