Caries
Poojan Shrestha, BDS, MSc (he/him/his)
Resident
Division of Pediatric and Public Health, Adams SoD, UNC-Chapel Hill
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
Poojan Shrestha, BDS, MSc (he/him/his)
Resident
Division of Pediatric and Public Health, Adams SoD, UNC-Chapel Hill
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States
Misa Graff, PhD
Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Yujie Wang, PhD
Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Yu Gu, BS
Gillings School of Global Public Health, University of North Carolina at Chapel Hill
John S. Preisser, PhD
Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Miguel A. Simancas-Pallares, DDS, MS, MSc
Adams School of Dentistry, University of North Carolina at Chapel Hill
Jeannie Ginnis, DDS
Adams School of Dentistry, University of North Carolina at Chapel Hill
Gary Slade, BDS, DDPH, PhD
Adams School of Dentistry, University of North Carolina at Chapel Hill
Kari North, PhD
Gillings School of Global Public Health, University of North Carolina at Chapel Hill
Kimon Divaris, DDS, PhD
Professor
Adams School of Dentistry, UNC-Chapel Hill
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, United States
Kimon Divaris, DDS, PhD
Professor
Adams School of Dentistry, UNC-Chapel Hill
University of North Carolina-Chapel Hill
Chapel Hill, North Carolina, United States
Scott W. Cashion, DDS MS
Associate Professor and Program Director
UNC Chapel Hill, Adams School of Dentistry
chapel Hill, North Carolina, United States
Purpose: Early childhood caries (ECC) is known to be influenced by social and behavioral factors. While individual susceptibility/genetic factors are strongly theorized, they remain largely unexplored. In this study, we sought to identify ECC-associated interactions between two strong ECC risk factors [sugary snacks/beverage (SSB) consumption frequency and sub-optimal fluoride exposure in home water] and human genetic polymorphisms.
Methods: Information on ~14 million polymorphisms was obtained in a genome-wide association study of ECC in a multi-ethnic, community-based cohort of 6,144 preschool-age children in North Carolina. ECC was measured by calibrated examiners using ICDAS criteria and the dmfs index. Daily SSB consumption frequency was obtained via a parent questionnaire, whereas optimal (≥0.60ppm) vs. sub-optimal ( < 0.60ppm) fluoride exposure was determined by home water samples measurement (EPA method 300.0). Genome-wide interactions were identified with 1- and 2-degree-of-freedom tests in linear mixed-models of dmfs adjusting for age, sex, race/ethnicity, population stratification, specifying a P < 5x10-8 statistical significance threshold.
Results: We identified 9 genome-wide significant loci, several of those with important and relevant functional roles, including variants in SLC41A3 (rs71327750, P=3.2x10-8) and RNF157 (rs117997344, P=2.6x10-8). Rs650314 (P=3.2x10-9) is 25KB upstream of PHOSPHO1, a gene involved in bone mineralization and implicated in childhood hypophosphatasia. Eight additional significant polymorphisms were found in sugar-stratified analyses, including rs144438881 (P=4.5x10-8), ~20Kb downstream of the known bitter taste receptor genes TAS2R3, TAS2R4, and TAS2R5.
Conclusions: This study offers novel evidence for gene-environment interactions in ECC that upon validation in additional populations could be leveraged in risk assessment and precision dentistry applications.