Open Access Research article

Genetic mapping of high caries experience on human chromosome 13

Erika C Küchler1, Kathleen Deeley1, Bao Ho1, Samantha Linkowski1, Chelsea Meyer1, Jacqueline Noel1, M Zahir Kouzbari1, Mariana Bezamat1, José M Granjeiro23, Leonardo S Antunes24, Livia Azeredo Antunes4, Fernanda Volpe de Abreu4, Marcelo C Costa5, Patricia N Tannure67, Figen Seymen8, Mine Koruyucu8, Asli Patir9, Juan C Mereb10, Fernando A Poletta1112, Eduardo E Castilla1112, Ieda M Orioli13, Mary L Marazita114 and Alexandre R Vieira11415*

Author Affiliations

1 Department of Oral Biology, University of Pittsburgh, 614 Salk Hall, Pittsburgh, PA, USA

2 Clinical Research Unit, Fluminense Federal University, Niterói, RJ, Brazil

3 Directory of Programs, National Institute of Metrology, Quality and Technology (INMETRO), Duque de Caxias, RJ, Brazil

4 Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, RJ, Brazil

5 Department of Pediatric Dentistry and Orthodontics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

6 Veiga de Almeida University, Rio de Janeiro, RJ, Brazil

7 Discipline of Cariology, School of Dentistry, Salgado de Oliveira University, Niterói, RJ, Brazil

8 Department of Pedodontics, Istanbul University, Istanbul, Turkey

9 Department of Pedodontics, Medipol Istanbul University, Istanbul, Turkey

10 ECLAMC at Hospital de Area El Bolson, Rio Negro, Argentina

11 ECLAMC (Latin American Collaborative Study of Congenital Malformations) at CEMIC (Center for Medical Education and Clinical Research), Buenos Aires, Argentina

12 Department of Genetics, Oswaldo Cruz Foundation, ECLAMC at INAGEMP-CNPq (National Institute of Population Medical Genetics), Rio de Janeiro, Brazil

13 ECLAMC at INAGEMP-CNPq (National Institute of Population Medical Genetics) in Department of Genetics, Institute of Biology, Center of Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

14 Center for Craniofacial and Dental Genetics, and Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA, USA

15 Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

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BMC Medical Genetics 2013, 14:116  doi:10.1186/1471-2350-14-116

Published: 5 November 2013



Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries.


Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals.


Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1. When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3. The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high caries experience (p = 0.046). No mutations were found in the highly conserved sequence.


Genetic factors contributing to caries experience may exist in 13q31.1. The rs17074565 is located in an intergenic region and is predicted to disrupt the binding sites of two different transcription factors that might be involved with caries experience. GR expression in saliva may be a biomarker for caries risk and should be further explored.

Caries; Genetics; Polymorphism; Oral health