# Vitamin D and Vitamin D Receptor Polymorphisms Relationship to Risk Level of Dental Caries
###### Abstract  
Dental caries is a multifactorial disease with multiple risk factors. Vitamin D levels (VDLs) and vitamin D receptor polymorphisms (VDRPs) have been investigated for this reason. The aim of this narrative review is to investigate the relation and the factors affecting vitamin D deficiency (VDD), VDRP, Early Childhood Caries (ECC) and Severe Early Childhood Caries (S-ECC) in children (primary and mixed dentition) and dental caries risk in adults (permanent dentition). Additionally, we present a model incorporating factors and interactions that address this relationship. Methods: Three databases (PubMed/MEDLINE, Web of Science, Cochrane Library) were comprehensively searched until 17 January 2023 using the following keywords: \"vitamin D\", \"vitamin D receptor polymorphism\", \"dental caries\", and \"dental caries risk\", finding 341 articles. Two reviewers searched, screened, and extracted information from the selected articles. All pooled analyses were based on random-effects models. Eligibility criteria were articles using dmft/DMFT diagnostic criteria with calibrated examiners, probability sampling, and sample sizes. We excluded studies conducted on institutionalized patients. A total of 32 studies were finally used. Results: In most studies, _Tadj, Folk,_ and _Bsml_ polymorphisms affected the prevalence of dental caries. A strong correlation between ECC, S-ECC, and the prevalence of dental caries was reported in association with VDD and maternal intake of VD in primary dentition. Regarding the influence in mixed dentition, the results were found to be inconclusive. A slight positive influence was reported for permanent dentition. Conclusions: Factors affecting caries risk were maternal intake, socioeconomic factors, and level of VD. There is a certain need for more well-conducted studies that will investigate the association between VDR gene polymorphisms and the prevalence of dental caries in mixed and permanent dentition, specifically in adult patients. v 2023 202  
Vitamin D deficiency (VDD) is defined when levels of 25(OH)D are below 20 ng/mL (50 nmol/L) and there is an insufficiency between 21-29 ng/mL (50-75 nmol/L) [4]. VDD has, therefore, abnormality in calcium, phosphorus, and bone metabolism [4] and is associated with increased risk of neoplastic, metabolic, and immune disorders [5; 6]. Tooth mineralization co-occurs to skeletal mineralization, so disturbances in mineral metabolism affect bone and teeth. As VD has a crucial role in tooth and bone mineralization, low levels of VD may lead to a defective and hypomineralized tooth [6]. The main mechanism related to severe VDD causes hypophosphatemia and hypocalcemia with secondary hyperparathyroidisms [7]. Hyperparathyroidism, in turn, stimulates renal production of 1,25(OH)2D and absorption of calcium in intestines. It increases bone turnover and may lead to increased serum levels of calcium ions and decreased serum levels of inorganic phosphate [8]. Therefore, proper mineralization of teeth is inhibited due to the loss of VD signaling pathways in tooth cells as concentrations of calcium ions and phosphate ions are low [9; 10; 11]. The biological activity of VD is modulated and modified by the vitamin D receptor (VDR) protein. VDR is responsible for the expression of many genes involved in cellular proliferation and differentiation, calcium-phosphate homeostasis, and immune response [12]. VDR is regulated by the VDR gene, whose polymorphisms affect the function of the VDR protein. Polymorphisms are genetic variations in non-coding parts of the gene (introns) or in the exonic parts of the DNA that influence at least 1% of the population [13]. Changes in introns do not influence the protein product but can modify the degree of gene expression. On the other hand, changes in exonic parts of the gene affect the protein sequence, except for synonymous polymorphisms, which are alterations in exonic parts that do not affect the protein structure [13].