Vitamin D status and VDR gene polymorphisms in patients with growth hormone deficiency: A case control Tunisian study.

Introduction: Growth Hormone Deficiency (GHD) is a rare disease marked by a complete or partial reduction in the production of growth hormone. Vitamin D deficiency is frequent and may be associated with several pathologies. However, the association between GHD and vitamin D deficiency has not been extensively studied. This study aimed to analyse VDR gene polymorphisms related to vitamin D status to ensure better care for patients with GHD. Material and methods: A case-control study was conducted at the Children's Hospital of Tunis in collaboration with the Farhat Hached's Hospital of Sousse, including patients with GHD and healthy subjects. Genetic analysis of the VDR gene polymorphisms was performed using PCR-RFLP technique. Haplotypes were examined with Haploview software, while statistical analyses were carried out using SPSS and R programming language. Results: Our study revealed significant differences in vitamin D (p = 0, 049) and calcium concentrations between patients and healthy subjects, which were lower in the GHD group (p = 0,018). A comparison of allelic and genotypic frequencies of the five polymorphisms indicated an association between the FokI polymorphism and GHD. Furthermore, significant difference was observed between the ApaI genotypes and PTH (p = 0,019) and ALP (p = 0,035). FokI genotypes were associated with phosphorus (p = 0,021). Additionally, One haplotype, CTAGT, exhibited a significant difference between the patients and healthy subjects (p = 0,002). Conclusion: Our study findings indicate that hypovitaminosis D is common among patients with GHD, even when undergoing treatment with rhGH. This underscores the critical importance of vitamin D supplementation during treatment.

Gene detection of VDR BsmI locus and its approteins, genes and growthplication in rational drug use in patients with osteoporosis.

Aim: This paper determines the polymorphism distribution of the VDR BsmI gene in 350 patients and provides medication recommendations for osteoporosis based on detection results. Materials & methods: Chi-square tests compared genotype and allele frequencies with other populations. Results: Genotype frequencies were 91.66 bb, 8.72 Bb and 0.21% BB, with allelic frequencies of 95.43 b and 4.57% B, adhering to Hardy-Weinberg equilibrium. These findings suggest that VDR gene polymorphisms, particularly at the BsmIlocus, play an essential role in bone health and osteoporosis treatment. Genotype-based drug selection reduced adverse reactions from 14 to two cases. Conclusion: These findings improve clinical treatment efficacy and guide rational drug use for osteoporosis patients.

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Association of VDR gene variant rs2228570-FokI with gestational diabetes mellitus susceptibility in Arab women.

Gestational diabetes mellitus (GDM) has been linked with adverse pregnancy outcomes. Vitamin D receptor (VDR) gene variants have been associated with diabetes mellitus susceptibility and related complications. This study assessed the association between VDR gene polymorphism (rs2228570) and GDM risk among pregnant Arab women. A total of 368 pregnant Saudi women who were screened for GDM at 24-28 weeks of gestation and genotyped for the VDR gene variant (rs2228570) were included in this cross-sectional study. Circulatory insulin levels, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and vitamin D (25(OH)D) were measured. There were 108 women with GDM and 260 women without GDM. The genotype frequency of women with GDM was CC 60.2 %, CT 33.3 %, TT 6.9 %, and CT + TT 39.8 %; for non-GDM women, were CC 61.1 %, CT 31.5 %, TT 6.9 %, and CT + TT 38.4 %. No association was found between the VDR gene variant (rs2228570-FokI) and GDM susceptibility after adjustment for covariates. Serum 25(OH)D had a significant inverse association with FBG (r = -0.49, p = 0.01) and HbA1c (r = -0.45, p = 0.03) among carriers of the TT-genotype. Furthermore, a significant inverse correlation was observed between serum 25(OH)D and HOMA-ß (r = -0.20, p = 0.035) in individuals with the T-allele. Among pregnant Saudi women, glycemic indices appear to be influenced by vitamin D, suggesting a possible role it may play in mitigating the metabolic changes associated with GDM, particularly among individuals with specific genetic backgrounds. In our study population, rs2228570-FokI did not appear to be a significant contributor to GDM risk.

The Effect of Genetic Variations in the Vitamin D Receptor Gene on the Course of Depressive Symptoms.

BACKGROUND: Evidence on the association between single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and depressive symptoms is inconclusive. OBJECTIVES: The primary aim of the study was to investigate the association between SNPs in the VDR gene and depressive symptoms. METHODS: In a sample of older adults from the Longitudinal Ageing Study Amsterdam (n = 922), depressive symptoms were assessed using the Centre for Epidemiological Studies Depression scale (CES-D scale) at baseline and after 3, 6, and 10 y of follow-up. Blood samples for SNP and serum 25-hydroxyvitamin D3 (25(OH)D3) determination were obtained at baseline. The association between 13 SNPs in the VDR gene and the course of depressive symptoms were evaluated using linear mixed models. The interaction between SNPs and serum 25(OH)D3 in relation to depressive symptoms was evaluated using multiple linear regression. RESULTS: No SNPs were associated with the course of depressive symptoms. Significant interactions between serum 25(OH)D3 and SNPs in the VDR gene were found. Stratified analysis revealed that within the GG genotype strata, 10 nmol/L higher serum 25(OH)D3 was associated with 0.27 (95% CI: -0.50, -0.04) and 0.23 (95% CI: -0.48, 0.02) lower scores on the CES-D scale for Cdx-2 and 1b-G-886A, respectively. This association was not found in persons having the GA or AA genotype. CONCLUSIONS: No SNPs are associated with the course of depressive symptoms. Stratified analysis shows that the effect of serum 25(OH)D3 concentrations on depressive symptoms is different among genotypes of Cdx-2 and 1b-G-886A. Future research should elucidate on the function of Cdx-2 and 1b-G-886A to describe their effect.

The Relationship between VDR Gene Polymorphisms Bsm1 and Apa1 with Breast Cancer Risk.

Background In addition to its multifaceted physiological functions, vitamin D is recognized for its protective role against cancer. To manifest its effects, vitamin D engages with the vitamin D receptor ( VDR ) gene responsible for its encoding. Investigations have unveiled that polymorphisms within the VDR gene exert influence over the expression and/or functionality of the VDR protein. Notably, certain VDR gene polymorphisms have emerged as particularly pertinent in the context of tumorigenesis, including Fok1 (rs2228570), Bsm1 (rs1544410), Taq1 (rs771236), and Apa1 (rs7975232). This study aims to scrutinize the correlation between the Bsm1 and Apa1 polymorphisms and the susceptibility to breast cancer development. Materials and Methods In this study, 50 patients suffering from breast cancer with less than 6 months breast cancer diagnosis and 50 healthy control individuals have been chosen. Restriction fragment length polymorphism polymerase chain reaction was used to determine the genotype of polymorphisms. Results The results of the statistical analysis showed that among the studied polymorphisms, there was no correlation with the development of breast cancer. Conclusion Studies on various cancers have produced inconsistent results regarding vitamin D's role in the development and progression of cancer. Therefore, further research is necessary to determine vitamin D's role in cancer development and progression.

Association of vitamin D-binding protein polymorphisms and serum 25(OH)D concentration varies among Chinese healthy infants of different VDR-FokI genotypes: A multi-centre cross-sectional study.

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants.

Relevance of Serum Levels and Functional Genetic Variants in Vitamin D Receptor Gene among Saudi Women with Gestational Diabetes Mellitus.

Background: This study explored the association between ApaI-TaqI Single Nucleotide Polymorphisms (SNPs) in a Vitamin D receptor (VDR) and the risk of Gestational Diabetes Mellitus (GDM) in Saudi women, along with the serum levels of vitamin D. Methods: Ninety women with GDM and 90 non-GDM women were enrolled, based on the inclusion and exclusion criteria for pregnant women enrolled in a single-center study. Blood samples were retrieved from 180 pregnant women using ethylenediaminetetraacetic acid (EDTA) tubes. Serum samples were used to measure the vitamin D, 25-hydroxyvitamin D (25(OH)D or calcidiol), and lipid profiles. Blood was used to measure the hemoglobin A1c levels and to isolate the DNA. The polymerase chain reaction (PCR) was performed for the ApaI (rs79785232), BsmI (rs1544410), FokI (rs2228570), and TaqI (rs731236) SNPs in the VDR gene using restriction fragment length polymorphism analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed between the patients with and without GDM using various statistical software packages. Results: The Hardy-Weinberg equilibrium analysis was statistically significant (p > 0.05). The ApaI, BsmI, and TaqI SNPs were associated with alleles, genotypes, and different genetic models (p < 0.05). Vitamin D levels were associated with deficient levels (p = 0.0002), as well as with a normal and overweight body mass index (p = 0.0004). When vitamin D levels were measured with GDM covariates, the fasting plasma glucose (FPG) (p = 0.0001), postprandial blood glucose (PPBG) (p < 0.0001), oral glucose tolerance test (OGTT)-1 h (p = 0.005), high-density lipoprotein (p = 0.022), and low-density lipoprotein cholesterol (LDLc) (p = 0.001) levels were significantly different. When similar vitamin D levels were measured for each genotype, we confirmed that the ApaI SNP was associated with sufficient levels (p < 0.0001), whereas the BsmI, FokI, and TaqI (p < 0.05) were associated with insufficient levels. The logistic regression model confirmed that the first hour of the OGTT (p = 0.005) was strongly associated with GDM, whereas the analysis of variance confirmed that FPG and PPBG (p < 0.05) were strongly associated with all the SNPs evaluated in the VDR gene. Additionally, the second hour of the OGTT (p = 0.048) and LDLc (p = 0.049) were associated with the ApaI and FokI SNP. Moreover, the first hour OGTT (p = 0.045) and lipid profile parameters (p < 0.05) were associated. Haplotype analysis revealed positive associations among the examined SNPs, which seemed compatible with the hypothesis that variants and combinations of multiple SNP genotypes enhance the risk of GDM in women. Haplotype analysis revealed that different combinations of alleles, such as AGCC, CATT, CGTC, AGTC, and CATT (p < 0.05), were strongly associated. The linkage disequilibrium (LD) analysis showed a strong association with all combinations (p < 0.05). Among the gene-gene interactions, all possible combinations showed a positive association (p < 0.05). Conclusions: Low vitamin D levels were observed in women with GDM. The ApaI, BsmI, and TaqI SNPs were associated with genotype and allele frequencies (p < 0.05). Vitamin D and the SNPs in the VDR gene were associated, according to the ANOVA, logistic regression, haplotype analysis, LD analysis, and the generalized multifactor dimensionality reduction model (p < 0.05).

Increased susceptibility to complicated pneumonia among egyptian children with FokI (rs2228570), not TaqI (rs731236), vitamin D receptor gene polymorphism in association with vitamin D deficiency: a case-control study.

BACKGROUND: Determining a genetic contribution to the development of complicated community-acquired pneumonia in children may help understand underlying pathogenesis. We aimed to investigate the association between two vitamin D receptor (VDR) gene polymorphisms, FokI and TaqI, and susceptibility to complicated pneumonia in Egyptian children compared to uncomplicated pneumonia. Associations with 25 hydroxy-vitamin D serum level were studied. METHODS: This was a case-control study that included 320 participants divided into 2 groups: patients and controls. The patients' group included 100 children hospitalized with complicated pneumonia and 100 with uncomplicated pneumonia. 120 age and sex-matched apparently healthy children served as controls. The VDR FokI and TaqI polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 25 hydroxy-vitamin D level was estimated in serum using ELISA. RESULTS: Regarding FokI, homozygous CC genotype was more common in complicated (52%) than uncomplicated pneumonia (28%) and controls (10%) (OR = 65; 95%CI (5.13-822.63), p < 0.001) and (OR = 4.3; 95%CI (0.7-27.16), p = 0.003), respectively. Children carrying C allele possessed 3 higher odds for complicated than uncomplicated pneumonia (OR = 3.08; 95%CI (1.33-7.14), p < 0.001). Heterozygous CT genotype increased susceptibility to complicated pneumonia (OR = 13.7; 95%CI (4.6-40.1), p < 0.001), not uncomplicated pneumonia (OR = 1.56; 95%CI (0.86-2.85), p = 0.145). Among complicated pneumonia, vitamin D level was lower in CC (6.92 ± 2.6ng/ml) than CT (9.55 ± 3.2 ng/ml) and TT genotype carriers (13.13 ± 3.6ng/ml) (p < 0.001). There was no significant difference between patients and controls as regards TaqI genotypes and alleles. CONCLUSION: In association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.

Impact of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism on the risk of developing preeclampsia.

Objective: Preeclampsia is a multifactorial disease characterized by high blood pressure and protein in the urine. In this study, we investigated the association of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism with the risk of developing preeclampsia. Methods: 25-hydroxyvitamin D was measured using High-performance Liquid Chromatography. Vitamin D binding protein and vitamin D receptor gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. Results: The control subjects have significant higher level of 25-hydroxyvitamin D (33.5 ± 1.194 ng/mL) relative to patients (23.97 ± 1.604 ng/mL) (p < 0.05). Vitamin D receptor rs1544410 and rs2228570 dominant model (GA + AA; TC + CC) showed significant higher risk of developing Preeclampsia (OR = 4.11, 95% CI = 0.62-27.09, p < 0.01; OR = 3.58, 95%CI = 0.78-16.38, p < 0.001 respectively). Similarly, vitamin D binding protein rs7041 and rs4588, dominant model (TG + GG; CA + AA) showed higher risk of preeclampsia development compared to control people (OR = 1.69, 95%CI = 0.35-8.19, p < 0.05; OR = 1.06, 95%CI = 0.25-4.44, p < 0.05 respectively). AA genotype of rs4588 of GC gene was significantly associated with 25-hydroxyvitamin D level in serum relative to CC and CA (p < 0.05). Conclusion: From our study, we can conclude that a low level of 25-hydroxyvitamin D, GC (rs1544410 and rs2228570), and VDR (rs4588 and rs7041) gene polymorphism is linked with an increased risk of developing preeclampsia.

Effect of vitamin D metabolites and gene expression of vitamin D receptor, and 1-alpha-hydroxylase related to the sperm quality.

The incidence of male fertility disorders has increased greatly due to various genetic and lifestyle factors. Recently, it has been hypothesized that vitamin D may be involved with idiopathic infertility. The goal of the study was to determine the effect and relationship between blood vitamin D metabolites, intracellular sperm vitamin D levels, and gene expression of 1-α-hydroxylase and VDR, with regard to semen quality. Seventy volunteers aged 25-45 were involved in the study. According to spermogram analysis, participants were stratified into normozoospermic control group, non-normozoospermic target group, and oligoasthenoteratozoospermic group. Vitamin D metabolites (total 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol) in blood and spermatozoa were determined by ELISA. Free and bioavailable 25-hydroxycholecalciferol were calculated using the Vermeulen equation. mRNA expression of VDR and 1-α hydroxylase was evaluated by qPCR. Free and bioavailable 25-hydroxycholecalciferol were significantly higher in the control group compared to the target group and compared to the oligoasthenoteratozoospermic group . Intracellular sperm 1,25-dihydroxycholecalciferol was higher in the control group compared to the target group. The mRNA levels of 1- α-hydroxylase were significantly higher in the control samples, while VDR expression was significantly higher in the target group. Significant positive correlations were established between free and bioavailable 25-hydroxycholecalciferol with sperm motility and morphology. Vitamin D metabolites in blood and intracellular sperm 1,25-dihydroxycholecalciferol seem to exert beneficial effects on sperm motility and morphology. Regarding sperm quality, these effects are more pronounced in the free and bioavailable 25OHD compared to the total 25OHD in blood. Higher expression of 1-α-hydroxylase likely leads to higher intracellular levels of 1,25-dihydroxycholecalciferol, which could contribute to sperm motility and morphology. Higher VDR expression may be a compensatory mechanism related to lower intracellular sperm 1,25-dihydroxycholecalciferol.

Differences in Chronic Low-Grade Inflammation and Metabolic Disturbances between VDR Genotypes in an Ethnically Homogenous Postmenopausal Female Population from Poland.

(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50-60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

Black skin color but not VDR gene represent a risk factor for low serum levels of vitamin D in self-declared black individuals.

BACKGROUND: The absorption of vitamin D occurs via two main pathways: first, through the biosynthesis in the skin under the exposure of UV from sunlight; and second, through the intake of certain foods. However, its levels can be influenced by both genetic and environmental factors, which can generate changes such as vitamin D deficiency (hypovitaminosis D), a condition that black adults have a high potential to suffer from. OBJECTIVE: The aim of this work is to study the association of skin color (self-reported: black, brown and white), food consumption, and the BsmI polymorphism in the vitamin D receptor gene (VDR) on serum levels of vitamin D in a group of adults. METHODS: This was a cross-sectional analytical study. Individuals in the community were invited to participate in the research and, After signing the informed consent, a structured questionnaire was applied containing identification data, self-declaration of race/color, and nutritional data (Food frequency questionnaire (FFQ) and 24 h); afterwards, blood was collected for biochemical analysis, vitamin D was measured by Chemiluminescence and RT-PCR was used to evaluate the BsmI polymorphism of the VDR gene. Data was analyzed using a statistical program (SPSS 20.0) and differences between groups using p < 0.05. RESULTS: A total of 114 persons was evaluated between black, brown and white individuals. It was found that a large part of the sample presents hypovitaminosis D, and blacks stand out with an average serum vitamin D level of 15.9 ng/dL. The group demonstrated that dietary intake of vitamin D is low, with the present study is a pioneer in associating the polymorphism of the VDR gene (BsmI) with the consumption of foods that are considered to have a higher content of vitamin D in their composition. CONCLUSION: The VDR gene does not represent a risk factor for the consumption of vitamin D in this sample, and it was found that the self-declaration of "black" skin color was an independent risk factor for low serum levels of vitamin D.

GENETIC FEATURES OF CHILDREN WITH IDIOPATHIC SHORT STATURE.

OBJECTIVE: The aim: To investigate the clinical and genetic characteristics of children with idiopathic short stature, taking into account the polymorphism of the vitamin D receptor (VDR) BsmI gene. PATIENTS AND METHODS: Materials and methods: Eighteen children diagnosed with of idiopathic short stature who were treated at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine¼ were examined. The following values were taken into account: the patient's sex and age, anthropometric data, vitamin D level in the blood (excluding summer months of patient recruitment), bone age, basal growth hormone (GH) level and its level after stimulation tests (clonidine, insulin), IGF-1 levels, blood levels of total and ionized calcium and VDR gene polymorphism. RESULTS: Results: The A allele carriers of the polymorphic locus BsmI (rs1544410) of the VDR gene are significantly associated with the risk of developing idiopathic short stature OR = 4.47 (95% CI 2.11-9.48; p <0.05). The risk of idiopathic short stature is significantly higher OR = 9.33 (95% CI 3.09-28.16; p <0.05) in children with the presence of the G/A genotype. Vitamin D deficiency (43.83 ± 6.47 nmol/l) was found in children with the BsmI polymorphic variant G/G VDR, and vitamin D insufficiency was found in children with BsmI polymorphic variants G/A and A/A VDR (58.14 ± 20.05 and 51.58 ± 22.84 nmol/l, respectively). CONCLUSION: Conclusions: The data obtained regarding the polymorphic locus BsmI (rs1544410) of the of VDR gene cannot exclude it's the involvement in the pathogenesis of idiopathic short stature.

Plasma 25-Hydroxyvitamin D Level and VDR Gene Single Nucleotide Polymorphism rs2228570 Influence on COVID-19 Susceptibility among the Kazakh Ethnic Group-A Pilot Study.

Low plasma levels of the vitamin D metabolite 25-hydroxyvitamin D [25(OH)D] and the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been associated with the body's susceptibility to infectious diseases, including COVID-19. In this pilot retrospective study, representatives of the Kazakh population (central Kazakhstan) were divided into groups based on the test for IgM and IgG for coronavirus infection. We compared the 25(OH)D plasma levels and concluded that the COVID-19-positive group values (25.17 ng/mL ± 16.65) were statistically lower (p = 0.0114) compared to the COVID-19-negative ones (35.58 ng/mL ± 20.67). There was no association between age, gender and 25(OH)D concentration within the groups (p > 0.05). The genotyping of rs2228570 was performed using a TaqMan Real-Time PCR assay. Allele C predominated among the COVID-19-negative participants and significantly reduced the likelihood of coronavirus infection (p < 0.0001; OR = 0.0804; 95% CI 0.02357-0.2798). There were no statistically significant differences in the frequencies of the A, G and T alleles in the studied groups (p > 0.05). The GG genotype of rs2228570 was associated with a 4.131-fold increased likelihood of COVID-19 infection (p = 0.0288; χ2 = 5.364; OR = 4.131; 95% CI 1.223-13.71). Comprehensive studies are required to determine whether low 25(OH)D plasma concentrations and genetic background represent a risk factor for COVID-19 infection.

Risk Factors of Incident Kidney Stones in Indian Adults: A Hospital-Based Cross-Sectional Study.

Background The diverse manifestations of urolithiasis provide very interesting epidemiological data. This has prompted various studies to look into the etiopathogenesis of renal stones, which is believed to be multifactorial, both exogenous and endogenous. VDR Fok1 is a risk factor for renal stone formation and could cause the formation of renal stones through the mechanism of crystal induction and crystallization in the urine. While a few recent studies have shown the role of heavy metals like cadmium and lead in the formation of renal stones, the current knowledge is still insufficient. Methods This case-control prospective study was conducted in Guru Teg Bahadur (GTB) Hospital, a tertiary care facility in Delhi with 30 cases and 30 controls. Patients visiting the department of surgery between November 2011 and April 2013 were enrolled in the study. Cases were defined as patients with renal stones diagnosed on the basis of history and radiological investigations. Controls were selected from the patients admitted to the department of surgery for reasons other than renal stones. The study protocol was approved by the Institutional Ethical Committee of the University College of Medical Sciences, GTB Hospital, Delhi. Written informed consent was obtained from all patients. A structured questionnaire was used to collect data. Metal levels were analyzed by an atomic absorption spectrophotometer (Shimadzu Flame AA-680, Shimadzu Corp., Kyoto, Japan) at Delhi University. The vitamin D receptor gene was measured using genomic DNA. Horizontal agarose gel electrophoresis was used for the quantification of the genomic DNA. Results There were 30 cases and 30 controls in the study. Stress was more prevalent among cases (63%) compared to controls (36%). Nearly 83% of cases had the ff allele of the Vitamin D receptor gene compared to 46% of controls. The median arsenic and lead levels were higher among cases compared to controls. In the unadjusted model of logistic regression, we found stressed patients had three times higher odds of developing renal stones compared to non-stressed patients (OR (95% CI): 2.98 (1.04-8.52); p=0.04). Similarly, patients with higher blood concentrations of arsenic and lead had higher odds of developing renal stones compared to those with lower concentrations.  Conclusions There was a definitive role of heavy metals, including lead, cadmium, and arsenic, seen with renal stones. A significant association was seen between the ff allele of VDR polymorphism (Fok1 enzymes) and patients with renal stones. Other parameters, including male and stress factors, seem to have an important role in renal stone formation.

Serum vitamin D levels and vitamin D receptor gene ApaI and TaqI polymorphisms in patients with morphea: a case-control study.

A uncommon inflammatory condition called morphea causes fibrosis in the skin and subcutaneous tissue. The key stages in the pathophysiology are vascular damage, immunological response, and fibrosis. Numerous research have examined the relationships between the immune system, fibrosis, and vitamin D, but the exact pathogenetic pathways of morphea remain poorly understood. The purpose of this study was to investigate serum 25(OH)D levels and the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the vitamin D receptor (VDR) in morphea patients. There were 48 age- and sex-matched controls and 41 morphea patients total. VDR polymorphisms were found using PCR tests and gel electrophoresis, and serum 25(OH)D levels were determined using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The patient group consisted of 37 females (90.2%) and 4 males (9.8%). The patients' mean age was 38.68 ± 17.54 years. In terms of VDR ApaI and TaqI polymorphisms, there was no discernible difference between the patient and control groups. TaqI polymorphism heterozygosity was discovered in all patients with progressive disease, and this finding was statistically significant (p = 0.012). Patients' mean serum 25(OH)D levels were 16.98 ± 11.55 ng/mL, while those in the control group were 18.02 ± 14.30 ng/mL. VDR polymorphisms, vitamin D levels, disease subtype, age of onset, and responsiveness to treatment did not significantly correlate. In our research, we discovered that TaqI polymorphism may be related to the severity of the disease and that the polymorphisms of the VDR ApaI and TaqI were not associated with morphea susceptibility.

Vitamin D Receptor Gene Polymorphisms Affect Osteoporosis-Related Traits and Response to Antiresorptive Therapy.

The present study analyzed the effect of vitamin D receptor (VDR) gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) on bone mineral density (BMD), biochemical parameters and bone turnover markers, fracture prevalence, and response to three types of antiresorptive therapy (estrogen-progesterone, raloxifene, and ibandronate) in 356 postmenopausal women from Slovakia. Association analysis revealed a significant effect of BsmI polymorphism on lumbar spine BMD, serum osteocalcin (OC), and ß-CrossLaps levels. While ApaI and Cdx2 polymorphisms were associated with OC and alkaline phosphatase, TaqI polymorphism affected all turnover markers. ApaI, TaqI, and BsmI genotypes increased the risk of spinal, radial, or total fractures with odds ratios ranging from 2.03 to 3.17. Each of therapy types evaluated had a beneficial effect on all osteoporosis-related traits; however, the VDR gene affected only ibandronate and raloxifene treatment. ApaI/aa, TaqI/TT, and BsmI/bb genotypes showed a weaker or no response to ibandronate therapy in femoral and spinal BMD. The impact of aforementioned polymorphisms on turnover markers was also genotype dependent. On the contrary, only TaqI and BsmI polymorphisms influenced raloxifene therapy, even only in lumbar spine BMD. These results point to the potential of using the VDR gene in personalized pharmacotherapy of osteoporosis.

Genotypic Spectrum and its Correlation with Alopecia and Clinical Response in Hereditary Vitamin D Resistant Rickets: Our Experience and Systematic Review.

Alopecia in hereditary vitamin D resistant rickets (HVDRR) has some correlation with severe rickets and poor overall response. However, these observations are based on small series. Hence, we aim to assess the genotypic spectrum of HVDRR and its correlation with alopecia and clinical response. Seven genetically-proven HVDDR patients from five unrelated families and 119 probands from systematic review were analysed retrospectively for phenotypic and genotypic data and overall response to therapy. In our cohort mean age at rickets onset was 12 (± 3.4) months. Alopecia was present in all patients but one. All patients had poor overall response to oral high-dose calcium and calcitriol and most required intravenous calcium. Genetic analyses revealed four novel variants. On systematic review, alopecia was present in majority (81.5%) and preceded the onset of rickets. Patients with alopecia had higher serum calcium (7.6 vs.6.9 mg/dl, p = 0.008), lower 1, 25(OH)2 D (200 vs.320 pg/ml, p = 0.03) and similar overall response to oral therapy (28.7% vs. 35.3%, p = 0.56). Alopecia was present in 51.4% of non-truncating (NT) ligand-binding domain (LBD) variants, whereas it was universal in truncating LBD and all DNA binding-domain (DBD) variants. Overall response to oral therapy was highest in LBD-NT (46.4%) as compared to 7.6% in LBD-truncating and 19% in DBD-NT variants. Among LBD-NT variants, those affecting RXR heterodimerization, but not those affecting ligand affinity, were associated with alopecia. Both alopecia and overall response have genotypic correlation. Age at diagnosis and overall response to oral therapy were similar between patients with and without alopecia in genetically proven HVDRR.

Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia.

BACKGROUND: Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. OBJECTIVE: The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. PATIENTS AND METHOD: In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. RESULTS: Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). CONCLUSION: This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

Vitamin D receptor (VDR) mRNA overexpression is associated with poor prognosis in breast carcinoma.

Purpose: The prognostic value of vitamin D receptor gene (VDR) expression in breast cancer development is unclear. Here, we aimed to investigate whether VDR expression can be used as a prognostic indicator of breast cancer. Methods: We used various public bioinformatics platforms: Oncomine, GEPIA, UALCAN, Kaplan-Meier plotter, UCSC XENA, bc-GenExMiner, WebGestalt, and STRING database. Results: We found that VDR was upregulated in breast cancer in comparison to normal tissues. Overexpression of VDR was significantly associated with worse overall survival in breast cancer. The expression of VDR was related to age, TNM stages, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, basal-like (PAM 50) status, triple-negative breast cancer (TNBC) status, and basal-like (PAM 50) & TNBC status (P < 0.05). Increased VDR expression in breast cancer was significantly associated with older age. The 5 hub genes for VDR were NCOA1, EP300, CREBBP, and RXRA. Conclusion: Our investigation offers hints about the prognostic role of VDR in breast cancer. The findings suggest that VDR expression might be used as a marker to determine a breast cancer patient's prognosis. Nevertheless, further validation is warranted.