ABSTRACT: Background:Early childhood caries is a multifactorial disease involving interactions between genetic and environmental risk factors. The aim of this study was to examine the effects of vitamin D receptor (VDR) gene polymorphisms and gene-environment interactions on the etiology of, and susceptibility to, caries in Chinese children aged 3-5 years. Methods:Children (n?=?549) were divided into three groups according to caries risk: high (decayed, missing, filled teeth (dmft) index?>?4; n?=?148), moderate (dmft?=?1-4; n?=?156), and caries-free (n?=?245). A questionnaire was designed to collect demographic information, dietary habits, and oral hygiene practices, and dental plaque samples were collected to test acidogenic activity of bacteria. Genomic DNA was extracted from the buccal mucosa, and the VDR polymorphisms rs7975232, rs1544410, rs11568820, rs10735810, and rs731236 were genotyped using TaqMan assays. Results:There were no differences among the caries risk groups in frequencies of the rs7975232, rs731236, rs1544410, or rs11568820 polymorphisms (? 2 test, P > 0.05); however, the frequency of the rs10735810 CC genotype was clearly higher in the high caries risk group than in the control and moderate caries risk groups (39.2%, 25.6%, and 30.6%, respectively; ? 2 test, P=0.028). In multivariate analysis of genotypes and behavioral factors, rs7975232, rs731236, rs1544410, rs11568820, and rs10735810 were not associated with deciduous tooth decay (? 2 test, P > 0.05). Conclusion:We conclude that these VDR polymorphisms cannot be used as markers for identification of Chinese children at increased risk of dental caries, when combined with environmental factors. Future studies are needed to replicate these initial findings and better assess the risk of caries in deciduous teeth.