Genetic Mapping of Dental Caries Susceptibility on Chromosome 5

OBJECTIVE: Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan using forty-six Filipino families have mapped three loci (5q13.3, 14q11.2, and Xq27.1) for low caries susceptibility and two loci (13q31.1 and 14q24.3) for high caries susceptibility. The purpose of this study was to fine map the 5q13.3 locus, which was linked to low caries susceptibility under a dominant model, in order to identify genetic contributors to low caries susceptibility. METHODS: Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT (Decayed, Missing due to caries, Filled Teeth) scores were recorded and DNA was extracted from all subjects. Fifty-three single nucleotide polymorphisms were selected in the interval 5q12.1 to 5q13.3 and analyzed by polymerase chain reaction using TaqMan chemistry. Association between low caries experience and alleles at each marker was tested with the program Family-Based Association Test (FBAT). Calculations of linkage disequilibrium were computed with the Graphical Overview of Linkage Disequilibrium (GOLD) software. RESULTS: Statistically significant association between the marker rs27565 in PART1 and low caries experience (p = 0.0007) was found. Also, markers in ZSWIM6 (rs7720894; p=0.004), CCNB1 (rs875459; p=0.004), and BTF3 (rs6862039; p=0.008) were also associated with low caries experience. Patterns of linkage disequilibrium between these regions ranged from weak to moderate. CONCLUSION: Results suggest that genetic factor(s) influencing caries susceptibility may exist on the chromosomal interval 5q12.1-5q13.3. This work is supported by NIH grant R01-DE018914.