Vitamin D and Vitamin D Receptor Polymorphisms Relationship to Risk Level of Dental Caries

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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, TaqI, FokI, and BsmI 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.

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Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.

Michael Holick, Neil C Binkley, Heike Bischoff-Ferrari … (2011)

The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

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Genetics and biology of vitamin D receptor polymorphisms.

André G. Uitterlinden, Yue Fang, Joyce B J van Meurs … (2004)

The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.

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From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health.

Anthony W Norman (2008)

New knowledge of the biological and clinical importance of the steroid hormone 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and its receptor, the vitamin D receptor (VDR), has resulted in significant contributions to good bone health. However, worldwide reports have highlighted a variety of vitamin D insufficiency and deficiency diseases. Despite many publications and scientific meetings reporting advances in vitamin D science, a disturbing realization is growing that the newer scientific and clinical knowledge is not being translated into better human health. Over the past several decades, the biological sphere of influence of vitamin D(3), as defined by the tissue distribution of the VDR, has broadened at least 9-fold from the target organs required for calcium homeostasis (intestine, bone, kidney, and parathyroid). Now, research has shown that the pluripotent steroid hormone 1alpha,25(OH)(2)D(3) initiates the physiologic responses of >/=36 cell types that possess the VDR. In addition to the kidney's endocrine production of circulating 1alpha,25(OH)(2)D(3,) researchers have found a paracrine production of this steroid hormone in >/=10 extrarenal organs. This article identifies the fundamentals of the vitamin D endocrine system, including its potential for contributions to good health in 5 physiologic arenas in which investigators have clearly documented new biological actions of 1alpha,25(OH)(2)D(3) through the VDR. As a consequence, the nutritional guidelines for vitamin D(3) intake (defined by serum hydroxyvitamin D(3) concentrations) should be reevaluated, taking into account the contributions to good health that all 36 VDR target organs can provide.