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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE018914-02
Application #
7935257
Study Section
Special Emphasis Panel (ZRG1-MOSS-K (09))
Program Officer
Harris, Emily L
Project Start
2009-09-20
Project End
2014-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2010
Total Cost
$374,963
Indirect Cost
Name
University of Pittsburgh
Department
Dentistry
Type
Schools of Dentistry
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Weber, Megan; Bogstad Søvik, Jenny; Mulic, Aida et al. (2018) Redefining the Phenotype of Dental Caries. Caries Res 52:263-271
Bezamat, Mariana; Deeley, Kathleen; Khaliq, Shahryar et al. (2018) Are mTOR and Endoplasmic Reticulum Stress Pathway Genes Associated with Oral and Bone Diseases? Caries Res 53:235-241
Eckert, Scott; Feingold, Eleanor; Cooper, Margaret et al. (2017) Variants on chromosome 4q21 near PKD2 and SIBLINGs are associated with dental caries. J Hum Genet 62:491-496
Küchler, Erika Calvano; Pecharki, Giovana Daniela; Castro, Myrella Lescio et al. (2017) Genes Involved in the Enamel Development Are Associated with Calcium and Phosphorus Level in Saliva. Caries Res 51:225-230
Maheshwari, Kanwal; Silva, Renato M; Guajardo-Morales, Leticia et al. (2016) Heat Shock 70 Protein Genes and Genetic Susceptibility to Apical Periodontitis. J Endod 42:1467-71
Bayram, Merve; Deeley, Kathleen; Reis, Maria F et al. (2015) Genetic influences on dental enamel that impact caries differ between the primary and permanent dentitions. Eur J Oral Sci 123:327-334
Abbaso?lu, Zerrin; Tanbo?a, ?lknur; Küchler, Erika Calvano et al. (2015) Early childhood caries is associated with genetic variants in enamel formation and immune response genes. Caries Res 49:70-7
Anjomshoaa, Ida; Briseño-Ruiz, Jessica; Deeley, Kathleen et al. (2015) Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries. PLoS One 10:e0143068
Romanos, Helena Freire; Antunes, Leonardo Santos; Lopes, Ludiana Barbosa et al. (2015) BMP2 Is Associated with Caries Experience in Primary Teeth. Caries Res 49:425-33
Dill, Alisa; Letra, Ariadne; Chaves de Souza, Letícia et al. (2015) Analysis of multiple cytokine polymorphisms in individuals with untreated deep carious lesions reveals IL1B (rs1143643) as a susceptibility factor for periapical lesion development. J Endod 41:197-200

Showing the most recent 10 out of 30 publications