Although caries is largely preventable, it remains the most common chronic disease of children age 5 to 17 years in the US, as well as in the rest of the world. Caries is related to three essential interactive factors: the host, represented by teeth and saliva;the oral microbial flora;and type of diet. The factors related to the host are under strong genetic control, but they are easily modified by the other factors. For that reason, hereditary aspects have generally been relegated to a minor position. We have generated preliminary data from our R21 DE16718 that shows different loci may contribute to caries susceptibility. Our work is the first genome wide scan performed to find caries susceptibility loci. In addition, we generated evidence that three enamel forming genes (ameloblastin, amelogenin and tuftelin-1) contribute to caries susceptibility in two case-control independent cohorts. To continue these studies, we propose the following specific aims: (1) Fine map the 2 loci that showed in our genome wide scan suggestive evidence to play a role in high caries susceptibility;(2) Fine map the 3 loci that showed in our genome wide scan suggestive evidence to play a role in low caries susceptibility;and, (3) Identify genetic variants in ameloblastin, amelogenin and tuftelin-1 that contribute to high caries susceptibility. For fine mapping, we will use single nucleotide polymorphisms at 0.5 to1 cM intervals. Genes will be chosen to enter the mutation search protocol based on the results of fine mapping studies (linkage + association). In addition, direct sequencing of ameloblastin, amelogenin and tuftelin-1 in individuals with high risk haplotypes is proposed. We hope these data will provide insight to new prevention and therapeutic strategies for caries.
The identification of genetic variation contributing to caries susceptibility can provide new insights to the causes of this highly prevalent disease. This new knowledge could provide the basis for suggesting genes to be used as new prevention strategies for caries.
|Shaffer, John R; Carlson, Jenna C; Stanley, Brooklyn O C et al. (2015) Effects of enamel matrix genes on dental caries are moderated by fluoride exposures. Hum Genet 134:159-67|
|Vieira, Alexandre R; Modesto, Adriana; Marazita, Mary L (2014) Caries: review of human genetics research. Caries Res 48:491-506|
|Weber, Megan L; Hsin, Hong-Yuan; Kalay, Ersan et al. (2014) Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay. BMC Med Genet 15:81|
|Halusic, Alina M; Sepich, Victoria R; Shirley, Daniel C et al. (2014) Calcium and magnesium levels in primary tooth enamel and genetic variation in enamel formation genes. Pediatr Dent 36:384-8|
|Küchler, Erika C; Feng, Ping; Deeley, Kathleen et al. (2014) Fine mapping of locus Xq25.1-27-2 for a low caries experience phenotype. Arch Oral Biol 59:479-86|
|Krasone, Kristýýne; Lace, Baiba; Akota, Ilze et al. (2014) Genetic variation in the promoter region of beta-defensin 1 (DEFB 1) is associated with high caries experience in children born with cleft lip and palate. Acta Odontol Scand 72:235-40|
|Shimizu, T; Deeley, K; Briseno-Ruiz, J et al. (2013) Fine-mapping of 5q12.1-13.3 unveils new genetic contributors to caries. Caries Res 47:273-83|
|Briseno-Ruiz, Jessica; Shimizu, Takehiko; Deeley, Kathleen et al. (2013) Role of TRAV locus in low caries experience. Hum Genet 132:1015-25|
|Kuchler, Erika C; Deeley, Kathleen; Ho, Bao et al. (2013) Genetic mapping of high caries experience on human chromosome 13. BMC Med Genet 14:116|
|Jeremias, Fabiano; Koruyucu, Mine; Kuchler, Erika C et al. (2013) Genes expressed in dental enamel development are associated with molar-incisor hypomineralization. Arch Oral Biol 58:1434-42|
Showing the most recent 10 out of 15 publications