Genetic and environmental factors associated with dental caries in children

Objectives: Dental caries, a multifactorial complex disease, remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes in caries. The purpose of this analysis was to assess genetic and environmental factors contributing to childhood caries using data from the Iowa Fluoride Study.

Methods: Environmental factors (age, sex, race, toothbrushing frequencies and water fluoride level) and three dental caries scores (dfs-total, dfs-pit/fissure, and dfs-smooth surface) were assessed in 575 unrelated children (age range 2.8 to 7.6, mean =5.2).  Logistic regression was applied to assess environment correlates. The Family Based Association Test (FBAT) was used to test associations between each of 25 SNPs (from 10 caries candidate genes) for 333 Caucasian parent-child trios.  Below are the numbers of children with each of the six caries traits analyzed in FBAT, three for the scores=0 (to detect protective-alleles against caries) and three for scores³1 (to detect risk-alleles for caries):

	Total	Pit/fissure	Smooth surface
dfs=0	251	263	282
dfs³1	82	70	51

Results: Among all covariates, age, toothbrushing frequencies and water fluoride level were statistically correlated to one or more of the three caries risk traits (P<0.1). SNPs in three genes (DSPP, KLK4, and AQP5) showed consistent associations with protection against caries, for all three caries scores (P<0.05). Notably, for KLK4, the results for the risk phenotypes (dfs scores³1) were consistent with the “protective” allele results for smooth surface caries, i.e. the opposite allele is associated with increased caries risk.   Besides, a SNP in MMP20 showed border-line association with risk for smooth surface caries (p=0.08). 

Conclusions: We identified associations of dental caries with multiple candidate genes and environmental factors.  All genes involved are important in enamel formation and tooth development (KLK4, MM20, DSPP) or salivary function (AQP5).

NIH grants R01-DE014889, R01-DE09551, R01-DE12101, M01-RR00059; Biosciences Advantage program 5R25GM058939-08.