Fine Mapping of 14q24.3, a Locus for High Caries Experience

Objective: 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, 14q24.3, and Xq27. Forty-six families with similar cultural, behavioral, oral hygiene habits, and fluoride exposure living in rural Philippines were studied. 

Method: In the present study, we aimed to fine map 14q24.3 in an expanded population data set of 72 families from the Philippines. This locus had suggestive linkage results (recessive single-point LOD score of 2.06) with high caries susceptibility on the studied population. We selected 97 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. Genotypes are in Hardy-Weinberg equilibrium. 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. 

Result: The results suggest that seven markers in ESRRB (estrogen-related receptor beta; rs745011, p=0.0003; rs1077430, p=0.03; rs2860216, p=0.0001; rs4903399, p=0.001; rs4903419, p=0.003; rs6574293, p=0.005; and rs10132091, p= 0.005) at 14q24.3 are associated with high caries experience. 

Conclusion:

These results suggest that we identified a new candidate gene for caries, which is likely involved in the development of salivary glands, specifically the parotid gland.