title: Genetic mapping of high caries experience on human chromosome 13.
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.
authors.forename: Erika C
authors.initials: EC
authors.lastname: Küchler
authors.forename: Kathleen
authors.initials: K
authors.lastname: Deeley
authors.forename: Bao
authors.initials: B
authors.lastname: Ho
authors.forename: Samantha
authors.initials: S
authors.lastname: Linkowski
authors.forename: Chelsea
authors.initials: C
authors.lastname: Meyer
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Noel
authors.forename: M Zahir
authors.initials: MZ
authors.lastname: Kouzbari
authors.forename: Mariana
authors.initials: M
authors.lastname: Bezamat
authors.forename: José M
authors.initials: JM
authors.lastname: Granjeiro
authors.forename: Leonardo S
authors.initials: LS
authors.lastname: Antunes
authors.forename: Livia Azeredo
authors.initials: LA
authors.lastname: Antunes
authors.forename: Fernanda Volpe
authors.initials: FV
authors.lastname: de Abreu
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Costa
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tannure
authors.forename: Figen
authors.initials: F
authors.lastname: Seymen
authors.forename: Mine
authors.initials: M
authors.lastname: Koruyucu
authors.forename: Asli
authors.initials: A
authors.lastname: Patir
authors.forename: Juan C
authors.initials: JC
authors.lastname: Mereb
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Poletta
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Ieda M
authors.initials: IM
authors.lastname: Orioli
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.affiliation: Department of Oral Biology, University of Pittsburgh, 614 Salk Hall, Pittsburgh, PA, USA. arv11@pitt.edu.
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D019295:Computational Biology; D004252:DNA Mutational Analysis; D003731:Dental Caries / Q000235:genetics; D005260:Female; D015894:Genome, Human; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010679:Philippines; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D014157:Transcription Factors