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GENETIC MAPPING OF HIGH CARIES EXPERIENCE ON HUMAN CHROMOSOME 13
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Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
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