Dioxin receptor gene AHR is associated with early childhood caries

Objectives: Early childhood caries (ECC) is a significant public health problem that has increased in recent years, affects a vulnerable non-autonomous population, and exhibits drastic disparities across demographic strata with the greatest disease burden concentrated in minority groups and rural populations. Environmental, microbial, and genetic factors are all hypothesized to impact risk of ECC. However, little is known about the specific genes that may contribute to ECC, or how genetic risk variants interact with environmental factors. Toward this end, we performed a pilot genome-wide association study to investigate the genetic basis of ECC.
Methods: A population-based cohort of families was ascertained by the Center for Oral Health Research in Appalachia. 270 children ages 1-5 years received intra-oral dental caries assessments, from which the decayed (including non-cavitated lesions) and filled surface (dfs) index, a quantitative ECC phenotype, was determined. 546,981 genetic polymorphisms assayed on an Illumina platform were interrogated for association with dfs while adjusting for the effects of age and sex.
Results: Two genomic loci were associated with dfs: microRNA MIR3974 on chromosome 12 (p=1.6E-7) and the dioxin (aryl hydrocarbon) receptor, AHR, on chromosome 7 (p=7.2E-6). MicroRNAs are important for regulating gene expression, although the target(s) of MIR3974 is unknown. AHR serves a variety of biological functions including regulating the host response to a number of environmental toxins such as aromatic hydrocarbons from cigarette smoke and environmental exposure to dioxins. Dioxin exposure, in particular, has detrimental effects specific to the development of dental tissues at otherwise non-toxic doses. These effects may be moderated by AHR.
Conclusions: AHR may constitute a novel dental caries risk gene that regulates the host response to cariogenic exposures including tobacco smoke and environmental dioxins. Additional work is needed to replicate the observed associations and determine the mechanism by which AHR contributes to the risk of ECC. R01-DE014899