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[This corrects the article DOI: 10.3389/fmed.2025.1657534.].

BackgroundAccumulating data have suggested that vitamin D receptor (VDR) gene is a pretender gene for vulnerability to Parkinson disease (PD). This study aimed to assess the relationship of VDR gene polymorphisms (FokI and ApaI) with PD. Fifty patients suffering from PD and 50 age- and sex-matched healthy controls were included. Unified Parkinson Disease Rating Scale (UPDRS) was done to assess disease severity. Genetic testing for VDR gene single nucleotide polymorphisms (FokI and ApaI) was done using real time polymerase chain reaction (PCR) technique.ResultsConcerning frequency of genes and alleles for vitamin D receptor gene polymorphisms (FokI and ApaI), no statistically significant difference was found between PD patients and controls. AC genotype was associated with younger age and younger age at onset of disease compared to CC and AA genotypes of ApaI gene polymorphisms. CC genotype was significantly positively correlated with fatigue and urine incontinence. VDR gene polymorphisms were not found to be independent predictors for severity of PD after adjustment for possible confounders.ConclusionVDR gene polymorphisms are related to the clinical manifestations rather than etiology or severity of idiopathic PD.

Background/Aim: Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are involved in a variety of biological processes including cell proliferation, apoptosis, and adhesion in malignant tumors. This study investigated whether vitamin D levels and genetic variations of VDR are risk factors for thyroid cancer. Patients and Methods: Patients who underwent surgery for differentiated thyroid carcinoma (n=113) and those with benign thyroid pathology (n=150) were genotyped for VDR gene polymorphisms (ApaI, TaqI, FokI, and BsmI) and their 25(OH)D levels were simultaneously measured. Demographic data and histopathologic reports were also acquired for all patients. Results: Vitamin D levels were significantly lower in the thyroid cancer group (p=0.03). FokI and TaqI polymorphisms were more frequent in the thyroid cancer patients (p<0.001). Compared to control, the proportion of the FokI Ff genotype was increased (p<0.0006) and the proportion of the TaqI Tt genotype was also higher among patients with thyroid cancer (p<0.0001). The Ff genotype of FokI was also associated with multifocality, invasive pattern, and risk for local metastasis. Conclusion: The VDR gene polymorphism FokI may be associated with the risk of thyroid cancer and its more aggressive forms.

Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) buildup and neuronal degeneration. An association between low serum vitamin D levels and an increased risk of AD has been reported in several epidemiological studies. Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D, and is generated in the kidney and many other tissues/organs, including the brain. It is a steroid hormone that regulates important functions like calcium/phosphorous levels, bone mineralization, and immunomodulation, indicating its broader systemic significance. In addition, calcitriol confers neuroprotection by mitigating oxidative stress and neuroinflammation, promoting the clearance of Aβ, myelin formation, neurogenesis, neurotransmission, and autophagy. The receptors to which calcitriol binds (vitamin D receptors; VDRs) to exert its effects are distributed over many organs and tissues, representing other significant roles of calcitriol beyond sustaining bone health. The biological effects of calcitriol are manifested through genomic (classical) and non-genomic actions through different pathways. The first is a slow genomic effect involving nuclear VDR directly affecting gene transcription. The association of AD with VDR gene polymorphisms relies on the changes in vitamin D consumption, which lowers VDR expression, protein stability, and binding affinity. It leads to the altered expression of genes involved in the neuroprotective effects of calcitriol. This review summarizes the neuroprotective mechanism of calcitriol and the role of VDR polymorphisms in AD, and might help develop potential therapeutic strategies and markers for AD in the future.

The vitamin D receptor (VDR) belongs to the nuclear receptor superfamily of transcription factors. The VDR is expressed in diverse brain regions and has been implicated in the neuroprotective, antiaging, prosurvival, and anti-inflammatory action of vitamin D. Accordingly, a relationship between vitamin D insufficiency and susceptibility to neurodegenerative diseases has been suggested. However, due to the multitargeted mechanisms of vitamin D and its often overlapping genomic and nongenomic effects, the role of the VDR in brain pathologies remains obscure. In this narrative review, we present progress in deciphering the molecular mechanism of nuclear VDR-mediated vitamin D effects on prosurvival and anti-inflammatory signaling pathway activity within the central nervous system. In line with the concept of the neurovascular unit in pathomechanisms of neurodegenerative diseases, a discussion of the role of the VDR in regulating the immune and vascular brain systems is also included. Next, we discuss the results of preclinical and clinical studies evaluating the significance of vitamin D status and the efficacy of vitamin D supplementation in the treatment of Parkinson’s and Alzheimer’s diseases, emphasizing the possible role of the VDR in these phenomena. Finally, the associations of some VDR polymorphisms with higher risks and severity of these neurodegenerative disorders are briefly summarized.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development. The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal. A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history. SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms. Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.

BackgroundOral Squamous Cell Carcinoma (OSCC) arises through an intricate interplay of underlying genetic traits and surrounding environmental conditions. Variations in the vitamin D receptor (VDR) gene, particularly single-nucleotide polymorphisms (SNPs), may contribute to individual susceptibility and disease progression.ObjectiveTo conduct a systematic review evaluating the role of VDR gene polymorphisms in influencing susceptibility to OSCC.MethodsA systematic literature search was performed in PubMed, Scopus, and Google Scholar to identify human case-control studies evaluating VDR SNPs in relation to OSCC. The methodological quality and potential bias of the selected studies were assessed using the Newcastle-Ottawa Scale (NOS). Due to substantial heterogeneity among the studies in terms of population characteristics, genotyping methods, and outcome measures, a meta-analysis was not performed, and the findings were summarized descriptively.ResultsFrom an initial pool of 90 records, five case-control studies met the inclusion criteria. Qualitative synthesis revealed consistent associations between polymorphisms in the VDR gene, particularly Fok1 (rs2228570), TaqI (rs731236), and ApaI (rs7975232), and in the CYP24A1 (rs2296241) gene, which encodes a VDR-regulated enzyme involved in the catabolism of active vitamin D metabolites. These variants have also been explored for their potential association with oral potentially malignant disorders (OPMDs), including leukoplakia, oral submucous fibrosis, and oral erythroplakia, which may undergo malignant transformation to OSCC. Most of the included studies demonstrated a low risk of bias and supported the role of these SNPs in OSCC susceptibility, as well as their potential prognostic relevance.ConclusionVDR polymorphisms may contribute to OSCC risk by affecting immune and cellular pathways. Although findings are promising, larger, multi-ethnic studies are needed to confirm their clinical significance.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251105619, PROSPERO CRD420251105619.

This systematic review examines the relationship with multiple myeloma (MM) risk for sunlight and vitamin D related exposures, including vitamin D supplementation, circulating 25-hydroxyvitamin D concentration, personal ultraviolet B radiation exposure, ambient solar irradiance and vitamin D receptor (VDR) gene polymorphisms We conducted a search for terms related to multiple myeloma, vitamin D, vitamin D receptor, ultraviolet radiation, sunlight, and single nucleotide polymorphism (SNP) using Ovid MEDLINE, Ovid EMBASE, Web of Science and Cochrane CENTRAL. Studies were assessed for risk of bias and quality using the RoB 2.0, ROBINS-E or Q-Genie tools. We identified 13 eligible studies: one randomised controlled trial, two cohort studies, and ten case-control studies, including one nested case-control study and one meta-analysis of genome-wide association studies. We conducted a qualitative synthesis; quantitative synthesis was not appropriate due to study heterogeneity and the small number of studies identified. There was insufficient evidence to support an effect of any sunlight or vitamin D related exposure on MM risk. No polymorphisms in VDR were found to be strongly related to risk for people of European ancestry. Of the identified studies, many had high risk of bias or were of lower quality. Few studies have investigated the association between sunlight and vitamin D related exposures and multiple myeloma risk. The scarcity of high-quality studies makes it difficult to evaluate potential effects of these exposures on MM risk. Further research is necessary to investigate the influence of vitamin D related exposures on risk of multiple myeloma.. •No large effects identified for common VDR gene variants in European populations.•Inadequate evidence to support an effect of vitamin D supplementation on MM risk.•Evidence on circulating 25 hydroxy vitamin D, UVR exposure and MM risk inconsistent.

Intolerance to dairy products resulting from the abnormal digestion of milk sugar (lactose) is a common cause of human gastrointestinal disorders. The aim of this study was to show that the -13910 C>T LCT gene polymorphism, together with genotypes of selected VDR gene polymorphisms and diet and nutritional status parameters, can impact the prevalence of vitamin D and calcium deficiency in young adults. This study was conducted on a group of 63 people, which comprised 21 individuals with primary adult lactase deficiency, and a control group of 42 individuals with no hypolactasia. The LCT and VDR gene genotypes were assessed using PCR restriction fragment length polymorphism (PCR-RFLP) analysis. A validated HPLC method was used to determine serum concentrations of 25(OH)D2 and 25(OH)D3. Atomic absorption spectrometry was used to determine calcium levels. Their diets (self-reported 7-day estimated food record), estimated calcium intakes based on the ADOS-Ca questionnaire and basic anthropometric parameters were assessed. The CC genotype associated with hypolactasia was found in 33.3% of the subjects. The presence of the CC variant of the LCT gene polymorphism in the study group of young Polish adults was found to be associated with significantly lower milk (134.7 ± 66.7 g/d vs. 342.5 ± 176 g/d; p = 0.012) and dairy product consumption (78.50 ± 36.2 g/d vs. 216.3 ± 102 g/d; p = 0.008) compared with lactase persistence. At the same time, people with adult-type primary intolerance were found to have statistically significant lower serum levels of vitamin D and calcium (p < 0.05). There was a higher chance of vitamin D and calcium deficiency and a lower intake in the group exhibiting lactase non-persistence (OR > 1). The AA variant of the VDR gene’s BsmI polymorphism present in people with hypolactasia may further contribute to an increased risk of vitamin D deficiency. Exclusion of lactose from the diet, combined with impaired vitamin D metabolism, may also lead to inhibited calcium absorption by the body. Further research should be carried out on a larger group of subjects to clarify the relationship between lactase activity and vitamin D and calcium levels in young adults.

Patients with systemic sclerosis (SSc) have a disproportionately high prevalence of reduced bone mineral density (BMD). Polymorphisms of the vitamin D receptor (VDR) gene have been associated with osteoporosis in patients with autoimmune diseases. The aim of this study was to investigate the prevalence and possible effects of VDR polymorphism on BMD and bone metabolism in patients with SSc. In patients with SSc measurement of BMD was performed using dual-energy X-ray absorptiometry. VDR polymorphisms (FokI, BsmI) were genotyped using restriction fragment length polymorphism analysis. Markers of bone metabolism (calcium, osteocalcin, β-crosslaps) were determined. Primary endpoint was the prevalence of VDR gene polymorphisms and the association with reduced BMD. Secondary endpoints included associations between bone metabolism and VDR gene polymorphism. 79 Caucasian patients with SSc were included. Overall, 83.5% had reduced BMD (51.9% osteopenia, 31.6% osteoporosis). The prevalence of VDR gene polymorphism (73% BsmI, 77% FokI) was comparable to studies in healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. Fokl polymorphism was significantly associated with reduced CTX levels, although changes remained within the reference limits. VDR polymorphisms can frequently be found in patients with SSc in comparable prevalence to healthy and rheumatic populations. The homozygous presence of FokI polymorphism, but not BsmI, was significantly associated with reduced axial BMD. This could be a possible contributor for the high prevalence of reduced BMD in 83.5% of patients with SSc in this study. Trial registration . DRKS00032768, date: 05.10.2023, retrospectively registered.