Fine Mapping of 14q11.2, a Locus for Low Caries Experience

Objectives: Caries is a multifactorial infectious disease characterized by destruction of the hard structures of the tooth. Factors predisposing to caries include the host, represented by teeth and saliva, the oral microbial flora, and type of diet, which can lead to chemical destruction associated with the intake of sugars and acids in food and drinks. In our previous genome wide scan study, we detected five loci related to caries susceptibility: 5q13.3, 13q31.1, 14q11.2, 14q 24.3, and Xq27. Forty-six families with similar cultural, behavioral, oral hygiene habits, and fluoride exposure living in rural Philippines were studied. Methods: In the present study, we aimed to fine map 14q11.2 in an expanded population data set of 72 families from the Philippines. This locus had suggestive linkage results (recessive single point LOD score of 2.29) with low caries susceptibility on the studied population. We selected 39 single nucleotide polymorphism markers spanning the candidate region. Those markers were chosen based on allele frequencies, gene structure, and patterns of linkage disequilibrium and haplotype blocks. At this moment we have genotyped the first 20 genetic markers. Genotypes are in Hardy-Weinberg equilibrium and the software package Family-Based Association test (FBAT) was used to determine the presence of possible overtransmission of alleles under a recessive model. P-values lower than 0.05 are considered statistically significant. Results: The preliminary results suggest that markers in TRAJ17 (T-cell receptor alpha joining 17; rs1997533, p=0.02; rs1997532, p=0.04; and rs7150049, p=0.02) at 14q11.2 are associated with low caries experience. Conclusions: These preliminary results suggest that we identified a new candidate gene for caries, which is likely involved in host immune response. Genotyping the remaining markers in the region is ongoing. This project is supported by NIH Grant R01 DE018914.