Genetic association of the BsmI variant of vitamin D receptor gene with risk of morbid obesity.

OBJECTIVE: The aim of this study was to evaluate the vitamin D receptor (VDR) BsmI variant in morbidly obese patients compared with healthy normal controls. METHODS: The study included 103 patients with morbid obesity and 120 healthy individuals serving as normal controls. The DNA samples obtained from blood were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The gender, age, smoking status, triglycerides, total cholesterol, insulin, mean body mass index, and frequency of allele and genotype of the BsmI variant in the VDR gene in morbidly obese patients were evaluated. RESULTS: The body mass index of the patients was 47.14 ± 7.19. The VDR B/B, B/b, and b/b genotype frequencies were 27.2% versus 28.3%; 54.4% versus 50%; and 18.4% versus 21.7% in the morbidly obese patients and the control group, respectively. There was no statistically significant difference between patients and control subjects in the genotype and allele distribution of the VDR BsmI variant (p>0.05). Both patients and control genotype frequencies are consistent with Hardy-Weinberg equilibrium. CONCLUSION: The BsmI variant in the VDR gene may not seem to predispose to morbid obesity in our study population. Further studies with a larger number of subjects are needed to make a more precise evaluation of this relationship.

Association of defects of enamel with polymorphisms in the vitamin D receptor and parathyroid hormone genes.

This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.

Zika virus infection suppresses CYP24A1 and CAMP expression in human monocytes.

Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.

Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis.

BACKGROUND: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. METHODS: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software. RESULTS: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). CONCLUSION: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.

Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization. / Variantes genéticas asociadas con la vitamina D en la población brasileña: investigación de potenciales instrumentos para aleatorización mendeliana

INTRODUCTION: Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population. OBJECTIVE: To examine genetic variants identified as determinants of serum vitamin D in genome-wide association studies of European populations and check whether the same associations are present in Brazil. If so, these single nucleotide polymorphisms (SNPs) could be developed locally as proxies to use in genetically informed causal inference methods, such as Mendelian randomization. MATERIALS AND METHODS: We extracted SNPs associated with vitamin D from the genomewide association studies catalog. We did a literature search to select papers ascertaining these variants and vitamin D concentrations in Brazil. RESULTS: GC was the gene with the strongest association with vitamin D levels, in agreement with existing findings in European populations. However, VDR was the most investigated gene, regardless of its non-existing association with vitamin D in the genomewide association studies. CONCLUSIONS: More research is needed to validate sound proxies for vitamin D levels in Brazil, for example, prioritizing GC rather than VDR.

Introducción. La vitamina D es necesaria para el metabolismo óseo y mineral, y participa en la regulación de la respuesta inmunitaria. También está relacionada con enfermedades crónicas en poblaciones europeas. En Brasil, existe una prevalencia elevada de deficiencia e insuficiencia de vitamina D, a pesar de la amplia disponibilidad de luz solar. Por lo tanto, es importante investigar el papel de la vitamina D como factor de riesgo de diversas enfermedades y establecer relaciones causales entre los niveles de vitamina D y los problemas de salud en la población brasileña. Objetivo. Examinar variantes genéticas relacionadas con la vitamina D sérica en estudios de asociación genómica de poblaciones europeas y comprobar si estas mismas están presentes en Brasil. De ser así, estos SNPs podrían utilizarse como proxies en métodos de inferencia causal, tales como la aleatorización mendeliana. Materiales y métodos. A partir del catálogo de estudios de asociación de genoma completo se extrajeron SNPs relacionados con los niveles de vitamina D. Luego se hizo una búsqueda bibliográfica para identificar los artículos que evaluaran estos SNPs y la concentración de vitamina D en Brasil. Resultados. GC fue el gen más fuertemente asociado con los niveles de vitamina D, en concordancia con los resultados existentes en poblaciones europeas. Sin embargo, el gen VDR fue el más investigado, aunque no esté vinculado con la vitamina D en los estudios de asociación de genoma completo. Conclusiones. Se necesita más investigación para validar proxies genéticos de los niveles de vitamina D en Brasil y se recomienda priorizar el gen GC en lugar de VDR.

Vitamin D receptor gene polymorphisms role in COVID-19 severity: Results of a Mexican patients' cohort.

Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged.

The role of interaction between vitamin D and VDR FokI gene polymorphism (rs2228570) in sleep quality of adults.

To evaluate association of vitamin D with sleep quality in adults and the influence of VDR-gene polymorphism FokI (rs2228570;A > G). Cross-sectional population-based study in adults, conducted in Brazil. The outcome was sleep-quality, evaluated by the Pittsburgh Sleep Quality Index. Vitamin D was determined by indirect electrochemiluminescence and classified as deficiency (VDD), 25(OH)D < 20 ng/mL in a healthy population or 25(OH)D < 30 ng/mL for groups at risk for VDD. FokI polymorphism in the VDR-gene was genotyped by qPCR and classified as homozygous wild (FF or AA), heterozygous (Ff or AG), or homozygous mutant (ff or GG). Multivariate logistic analysis was used to estimate the association between vitamin D and FokI polymorphism with sleep-quality. In a total of 1674 individuals evaluated, 53.6% had poor-sleep-quality, 31.5% had VDD, and the genotype frequency of the FokI polymorphism was 9.9% FF, 44.6% Ff, and 45.5% ff. In multivariate analysis, individuals with VDD had 1.51 times the chance of poor-sleep-quality, and individuals with the ff genotype had 1.49 times the chance of poor-sleep-quality (OR:1.49;95%CI:1.05-2.12) when compared to individuals with the FF or Ff genotype. In the combined analysis, individuals with VDD and ff genotype had more chance of poor-sleep-quality than individuals with sufficient vitamin D and genotype Ff or FF (OR:2.19;95%CI:1.27-3.76). Our data suggest that VDD and VDR FokI gene polymorphism are associated with poor-sleep-quality, and combining the two factors increases the chance of poor-sleep-quality compared to separate groups.

Interaction between Fokl polymorphism and vitamin D deficiency in the symptoms of mental disorders in adults: a population-based study.

Mental disorders are intricate and multifaceted and encompass social, economic, environmental, and biological factors. This study aimed to explore the potential association between vitamin D deficiency and anxiety and depression symptoms in adults, considering the role of the vitamin D receptor gene polymorphism FokI (rs2228570). This was a population-based cross-sectional study with stratified and cluster sampling, evaluating anxiety symptoms (AS) and depression symptoms (DS) in 1637 adults. Vitamin D levels were measured using electrochemiluminescence and were considered deficient when < 20 ng/mL in a healthy population or < 30 ng/mL in at-risk groups. Genotyping was performed using real-time polymerase chain reaction with TaqMan probes. The prevalence rates of AS, DS, and vitamin D deficiency were 23.5%, 15.8%, and 30.9%, respectively. No direct association was observed between vitamin D deficiency and AS or DS. However, interaction analysis revealed a combined effect of vitamin D deficiency and FokI for DS but not for AS. Individuals with vitamin deficiency and one or two copies of the altered allele of the FokI exhibited a higher prevalence of DS than individuals homozygous for the wild-type allele and vitamin D sufficiency. The interaction between vitamin D deficiency and the FokI polymorphism was associated with DS.

Single-nucleotide polymorphisms related to vitamin D metabolism and severity or mortality of COVID-19: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to verify the association between single-nucleotide polymorphisms (SNPs) in vitamin D-related genes and the severity or mortality of coronavirus disease 19 (COVID-19). We systematically searched PubMed, BVS/Bireme, Scopus, Embase, and Web of Science for relevant studies published until November 24, 2023. Twelve studies were included. Thirty-one SNPs related to four genes were studied (VDR, 13 SNPs; GC, 6 SNPs; DHCR7/NADSYN1, 6 SNPs; CYP2R1, 6 SNPs). Eight SNPs were examined in two or more studies (VDR rs731236, rs2228570, rs1544410, rs7975232, rs739837, rs757343, rs11568820, and rs4516035). Meta-analysis showed a significant association between the VDR rs1544410 Bb + bb genotype and b allele and an increased odds of developing severe/critical COVID-19 (Bb + bb vs. BB = 2 studies, OR = 1.73, 95% confidence interval (CI): 1.16-2.57, P = 0.007, I2 = 0%; b allele vs. B allele = 2 studies, OR = 1.31, 95% CI: 1.03-1.67; P = 0.03; I2 = 0%). Regarding the mortality rate, VDR rs731236 TT-genotype, TT + Tt genotype, and T allele; VDR rs1544410 bb-genotype, Bb + bb genotype, and b allele; VDR rs7975232 AA-genotype, AA + Aa genotype, and A allele; and VDR rs2228570 ff-genotype, Ff + ff genotype, and f allele were associated with increased odds of death due to COVID-19. In conclusion, the present study suggests that SNPs rs1544410 may serve as a predictive biomarker for COVID-19 severity and rs731236, rs1544410, rs7975232, and rs2228570 as predictive biomarkers for COVID-19 mortality. More well-designed studies involving a larger number of COVID-19 patients are required to validate and replicate these findings.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study / Associação de polimorfismos do gene do receptor de vitamina D com diabetes mellitus tipo 2 na população Taif: um estudo de caso-controle

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis ​​e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Genotype Prevalence of Lactose Deficiency, Vitamin D Deficiency, and the Vitamin D Receptor in a Chilean Inflammatory Bowel Disease Cohort: Insights from an Observational Study.

Lactose intolerance (LI) and vitamin D deficiency (VDD) have been linked to inflammatory bowel disease (IBD). We conducted an observational study in 192 Chilean IBD patients to investigate the prevalence of a specific gene variant (LCT-13910 CC genotype) associated with LI and the prevalence of VDD/Vitamin D Receptor (VDR) gene variants. Blood samples were analyzed using Illumina's Infinium Global Screening Array. The LCT-13910 CC genotype was found in 61% of IBD patients, similar to Chilean Hispanic controls and lower than Chilean Amerindian controls. The frequency of the LCT-13910-C allele in Chilean IBD patients (0.79) was comparable to the general population and higher than Europeans (0.49). Regarding VDR and VDD variants, in our study, the rs12785878-GG variant was associated with an increased risk of IBD (OR = 2.64, CI = 1.61-4.32; p-value = 0.001). Sixty-one percent of the Chilean IBD cohort have a genetic predisposition to lactose malabsorption, and a significant proportion exhibit genetic variants associated with VDD/VDR. Screening for LI and VDD is crucial in this Latin American IBD population.

Vitamin D Receptor and Retinoid X Receptor Alpha in Melanocytic Benign Lesions and Melanoma.

ABSTRACT: Vitamin D receptor (VDR) exerts its biological effects when it heterodimerizes to a nuclear receptor of the retinoid family called retinoid X receptor α (RXRα), stimulating or inhibiting DNA transcription. VDR stimulation by vitamin D analogs led to in vitro antiproliferative effects, and experimental RXRα knockout led to loss of proliferation control in melanoma cells. The aim of this study was to determine VDR and RXRα positivity in melanocytic lesions, compared with normal skin species. By immunohistochemistry assays, nuclear VDR, cytoplasmic VDR, and RXRα and RXRα in keratinocytes surrounding melanocytes were evaluated in 77 controls, 92 intradermal nevi, 54 dysplastic nevi, and 83 melanomas in this retrospective cross-sectional study. Nuclear VDR, cytoplasmic VDR, and RXRα were less expressed in exposed areas ( P < 0.001, P = 0.0006, and P < 0.001, respectively) than covered areas. All melanocytic lesions had loss of VDR and RXRα comparing with the control group. In the melanoma group, nuclear VDR tended to inversely correlate with the Breslow index (r = -0.11, P = 0.29) but directly correlated with histological regression ( P = 0.0293). RXRα inversely correlated with mitosis (r = -0.245; P = 0.0263). We can suggest that sun exposure affected VDR and RXRα immunopositivity. Nuclear VDR tendency of inverse correlation with the Breslow index showed that worse melanomas have a greater loss of VDR. RXRα inversely correlated with mitosis, indicating that RXRα can have a role in proliferation control. VDR and RXRα may participate in the development of melanocytic lesions and be a future target of new studies and directed therapies.

Vitamin D receptor gene polymorphisms influence on clinical profile and bone mineral density at different skeletal sites in postmenopausal osteoporotic women.

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age-matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A = 0.828 ± 0.09; A/G = 0.081 ± 0.13; G/G = 0.876 ± 0.12, p = .039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR] = 5.12, 95% confidence interval [CI ]= 1.13-23.27, p = .012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR = 0.24, 95%CI = 0.06-0.94, p = .029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD.

Bariatric Surgery and Vitamin D: Trends in Older Women and Association with Clinical Features and VDR Gene Polymorphisms.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. However, several complications were reported, such as vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS, and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

Association between genetic variants in key vitamin-D-pathway genes and external apical root resorption linked to orthodontic treatment.

This study evaluated the association between single-nucleotide polymorphisms (SNPs) in vitamin-D-related genes and the amount of external apical root resorption linked to orthodontic treatment. One hundred and forty-three individuals were assessed. The amount of external apical root resorption of upper central incisors (EARRinc ) and lower first molars (EARRmol ) were evaluated in radiographs. Seven SNPs were genotyped across four genes including the vitamin D receptor [VDR], group-specific component [GC], cytochrome P450 family 27 subfamily B member 1 [CYP27B1], and cytochrome P450 family 24 subfamily A member 1 [CYP24A1]. Linear regressions were implemented to determine allele-effects on external apical root resorption. Individuals carrying the AA genotype in VDR rs2228570 had a 21% higher EARRmol than those having AG and GG genotypes (95% CI: 1.03,1.40). EARRmol in heterozygous rs2228570, was 12% lower than for homozygotes (95%CI: 0.78,0.99). Participants with the CCG haplotype (rs1544410-rs7975232-rs731236) in VDR had an EARRmol 16% lower than those who did not carry this haplotype. Regarding CYP27B1 rs4646536, EARRinc in participants who had at least one G allele was 42% lower than for homozygotes AA (95%CI: 0.37,0.93). Although these results did not remain significant after multiple testing adjustment, potential associations may still be suggested. Further replication studies are needed to confirm or refute these findings.

Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis.

Although vitamin D (VD) is known to have multiple effects on the skin and immunity, its effects on atopic dermatitis (AD) severity remain unclear. We investigated whether oral cholecalciferol (VD3) supplementation changes stratum corneum expression of the vitamin D receptor (vdr), and the epidermal alarmins Cathelicidin Antimicrobial Peptide (camp/LL-37) and Thymic Stromal Lymphopoietin (tslp) in children with AD. We conducted an open-label supplementation study with weekly oral VD3 for six weeks in children with AD. Serum 25-hydroxyvitamin D (25OHD), lesional Staphylococcus aureus colonization, and AD severity evaluated by SCORAD index were evaluated before and after supplementation. Tape stripping (TS) was performed on non-lesional and lesional skin to measure mRNA expression of vdr, camp, and tslp through RT-qPCR and LL-37 peptide by ELISA. Twenty-two children with moderate-severe AD received weekly oral VD3 for six weeks. Total serum 25OHD increased from 45.1 ± 23 to 93.5 ± 24.3 nmoL/L (p < 0.0001), while SCORAD decreased from 41.4 ± 13.5 to 31.5 ± 15.8 (p < 0.0001). After treatment, epidermal gene expression of camp increased significantly in non-lesional (p = 0.014) and lesional (p = 0.0007) tape stripping samples, while vdr only increased in lesional skin samples (p < 0.0001). LL-37 peptide increased significantly only in lesional skin samples (p = 0.008). Gene expression of tslp did not change after oral VD3 treatment. In children with AD, oral VD3 supplementation was associated with improved VD status and AD severity, as well as increased VDR and Cathelicidin expression in lesional skin, which provide mechanistic clues on its effects.

Polymorphism but not methylation status in the vitamin D receptor gene contributes to oral mucositis in children.

OBJECTIVE: To investigate the relationship between the polymorphisms rs1544410 (BsmI), rs2228570 (FokI) and rs731236 (TaqI) and DNA methylation status in the VDR gene (vitamin D receptor) with oral mucositis (OM) in oncopaediatric patients treated with methotrexate (MTX®). METHODS: The population comprised healthy patients with haematological malignancies aged between 5 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, biochemical and haematological data were obtained from medical records. Genomic DNA from oral mucosal cells was used for the analysis of polymorphisms (n = 102) (PCR-restriction fragment length polymorphism) and DNA methylation (n = 81) (methylation-specific PCR). RESULTS: Males predominated (57.8%), and the mean age was 10.3 years (±4.7). OM affected 84.3% of patients, of which 53.1% developed severe oral mucositis (SOM). Patients with OM had lower platelet and leukocyte counts (p < 0.05). The G allele of rs1544410 (p = 0.040) and the CT genotype of rs2228570 polymorphisms were associated with SOM (p = 0.038). A partially methylated status in the VDR promoter was found in all patients. CONCLUSION: OM is associated with lower leukocyte and platelet counts. SOM is associated with the rs1544410 and rs2228570 polymorphisms. The methylation status of the VDR is not associated with inflammation or exposure to MTX®.

Association of CYP2R1 and VDR Polymorphisms with Metabolic Syndrome Components in Non-Diabetic Brazilian Adolescents.

Associations between vitamin D deficiency and metabolic syndrome (MS) have been reported; however, the underlying biological mechanisms remain controversial. The aim of this study was to investigate the associations of CYP2R1 and VDR variants with MS and MS components in non-diabetic Brazilian adolescents. This cross-sectional study included 174 adolescents who were classified as overweight/obese. Three CYP2R1 variants and four VDR variants were identified by allelic discrimination. The CYP2R1 polymorphisms, rs12794714 (GG genotype) (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.24-10.14, p = 0.023) and rs10741657 (recessive model-GG genotype) (OR = 3.90, 95%CI = 1.18-12.92, p = 0.026) were significantly associated with an increased risk of MS and hyperglycemia, respectively. The AG + GG genotype (dominant model) of the rs2060793 CYP2R1 polymorphism was associated with hyperglycemia protection (OR = 0.28, 95%CI = 0.08-0.92, p = 0.037). Furthermore, the CC genotype (recessive model) of the rs7975232 VDR polymorphism was significantly associated with a risk of hypertension (OR = 5.91, 95%CI = 1.91-18.32, p = 0.002). In conclusion, the CYP2R1 rs12794714 polymorphism could be considered a possible new molecular marker for predicting the risk of MS; CYP2R1 rs10741657 polymorphism and VDR rs7975232 polymorphism are associated with an increased risk of diabetes and hypertension in adolescents with overweight/obesity.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.