Vitamin D Receptor FokI Research Articles

Etiologic risk factors and vitamin D receptor gene polymorphisms in under one-year-old infants with urolithiasis.

The incidence of urinary tract stones in infancy has been increasing in Turkey. Risk factors and vitamin D receptor (VDR) gene polymorphisms were investigated in infants aged<1year who had stones. Forty infants with urinary tract stones and 80 infants without stones, aged<1year were enrolled in this study. Detailed surveys were taken of all infants, metabolic parameters and ApaI and FokI VDR gene polymorphisms were investigated. Infants with stones tended to be more commonly fed formula and multivitamins (vitamins A, C, D) (p<0.05). Positive family history came into prominence in the stony group (p<0.05). There were no significant differences in ApaI and FokI VDR gene polymorphisms between the groups with stones and the control groups. However, CA genotype of ApaI polymorphism was associated with family history and C allele of ApaI was related with family history and hypercalciuria (p<0.05). Hypercalciuria emerged as an underlying metabolic abnormality in the etiology of stones, and was observed at a rate of 38%. Infants who are given formula and multivitamins for vitamin D supplementation are at increased risk for the formation of urinary tract stones. VDR gene polymorphisms cause the formation of urinary tract stones and affect calcium (Ca) metabolism.

Association of Vitamin D Receptor (FokI and BsmI) Gene Polymorphism with Bone Mineral Density and Their Effect on 25-Hydroxyvitamin D Level in North Indian Postmenopausal Women with Osteoporosis.

Osteoporosis is a systemic disease with a strong genetic component. Vitamin D receptor (VDR) has been suggested as a candidate gene for osteoporosis. Therefore the present study was aimed to investigate the pattern of allelic variants of VDR gene polymorphism (FokI and BsmI), its influence on vitamin D levels and bone mineral density (BMD) in North Indian postmenopausal women with osteoporosis for possible genetic association. 254 postmenopausal osteoporotic women and 254 postmenopausal non osteoporotic women were included in the study. VDR FokI and BsmI gene polymorphism gene were assessed by the PCR-RFLP method. Serum 25-hydroxyvitamin D was measured by the ELISA. BMD at the L1-L4 lumbar spine, hip, forearm and femoral neck was assessed by dual energy X-ray absorptiometry. The average BMD at spine and hip in postmenopausal women with bb and spine, hip, femoral neck and forearm with ff genotype had significantly low BMD. The frequency of ff genotype and f allele was significantly higher in postmenopausal osteoporotic women when compared with postmenopausal non osteoporotic women. However, no significant association was found between the genotypes and vitamin D levels. Our study reveals that VDR gene FokI and BsmI polymorphism is significantly associated with low bone mineral density. Therefore the ff genotype and f allele of VDR FokI gene may be used as an important risk factor for osteoporosis.

Vitamin D Levels, Vitamin D Receptor Polymorphisms, and Inflammatory Cytokines in Aromatase Inhibitor-Induced Arthralgias: An Analysis of CCTG MA.27

BackgroundApproximately half of women taking aromatase inhibitor (AI) therapy develop AI-induced arthralgia (AIA), and many might discontinue AI therapy because of the pain. Using plasma samples from the MA.27 study, we assessed several factors potentially associated with AIA. Patients and MethodsMA.27 is a phase III adjuvant trial comparing 2 AIs, exemestane versus anastrozole. Within an 893-participant nested case-control AIA genome-wide association study, we nested a 72 AIA case-144 control assessment of vitamin D plasma concentrations, corrected for seasonal and geographic variation. We also examined 9 baseline inflammatory cytokines: interleukin (IL)-1β, IL-6, tumor necrosis factor-α, interferon (IFN)γ, IL-10, IL-12p70, IL-17, IL-23, and chemokine ligand (CCL)-20. Finally, we analyzed the multivariate effects of baseline factors: vitamin D level, previously identified musculoskeletal single nucleotide polymorphisms, age, body mass index, and vitamin D receptor (VDR) Fok-I variant genotype on AIA development. ResultsChanges in vitamin D from baseline to 6 months were not significantly different between cases and controls. Elevated inflammatory cytokine levels were not associated with development of AIA. The multivariate model included no clinical factors associated with AIA. However, women with the VDR Fok-I variant genotype were more likely to have a lower IL-1β level (P = .0091) and less likely to develop AIA after 6 months of AI compared with those with the wild type VDR (P < .0001). ConclusionIn this nested case-control correlative study, vitamin D levels were not significantly associated with development of AIA; however, patients with the Fok-I VDR variant genotype were more likely to have a significant reduction in IL-1β level, and less likely to develop AIA.

Genetic association analysis of vitamin D receptor gene polymorphisms and obesity-related phenotypes

Vitamin D has been established as a key factor in the development of obesity through the vitamin D receptor (VDR). The aim of this study was to investigate the contribution of the VDR gene to obesity-related phenotypes in a population of Caucasian young adults. The study population consisted of 701 healthy Spanish young adults (mean age 20.41±2.48). Three single-nucleotide polymorphisms (SNPs) of VDR (TaqI, BsmI and FokI) were selected as genetic markers. Body composition measurements including weight, body mass index (BMI), fat mass (FM), percentage of fat mass (PFM), fat-free mass (FFM) and visceral fat level (VFL) were analysed. Differences in obesity traits across the genotypes were determined using analysis of covariance (ANCOVA). The FokI polymorphism showed a significant association with PFM across the whole population after adjusting for age and sex (p=0.022). Age-adjusted analysis revealed an association between body weight and the TaqI and BsmI SNPs in males (p=0.033 and p=0.028, respectively). However, these positive findings did not remain significant after applying the Bonferroni correction for multiple testing. Our findings suggest that VDR genetic variants are unlikely to play a major role in obesity-related phenotypes in a population of Caucasian young adults.

VITAMIN D RECEPTOR (VDR) GENE POLYMORPHISM AND MATERNAL VITAMIN D DEFICIENCY IN INDIAN WOMEN WITH PRETERM BIRTH (PTB)

Objective: Preterm birth (PTB) is the leading cause of high infant mortality and long-term disability in young children worldwide. Array of adverse maternal and fetal outcomes linked with vitamin D level and its associated vitamin D receptor (VDR) gene. We undertook this study to investigate the association between VDR gene polymorphism with vitamin D deficiency and PTB in West Indian pregnant women.Methods: A total of 72 women with PTB and 138 healthy mothers with uncomplicated normal delivery were selected from different regions of Gujarat, India. FokI and TaqI single nucleotide polymorphism (SNP) of VDR gene determined by polymerase chain reaction and restriction fragment length polymorphism. Vitamin D level was determined using enzyme-linked immunosorbent assay.Result: ff genotype (29.17% vs. 10.87%, p=0.002) and f allele (49.31% vs. 35.51%, p=0.006) frequency distributions of VDR FokI showed significantly (odds ratio=0.566, 95% confidence interval=0.368-0.870, p=0.006) higher in women with preterm delivery than in control full term group. Genotype frequency of VDR TaqI showed no significant difference between preterm group and control.Conclusion: These results confirmed that women carrying ff genotype of FokI gene had significantly higher risk for vitamin D deficiency which enhances the risk of prematurity than women carrying FF genotype in West Indian women.

Genetic analysis of the Vitamin D receptor start codon polymorphism (FokI) in cervical vertebra and lumbar spine pathologies: a meta-analysis.

BackgroundVitamin D receptor (VDR) FokI polymorphism has been reported to influence the risk of spinal diseases. However, several studies suggest inconsistent results. Therefore, we performed this analysis to reveal the accurate relationship between VDR FokI polymorphism and spinal diseases.Materials and Methods8 articles accord with the strict inclusion and exclusion criteria. 1116 cases and 1263 controls are entered into this analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CI) are calculated to evaluate the association between VDR gene polymorphism and spinal diseases.ResultThe results suggest that allele F is a risk factor for spinal diseases and the difference is significant (F vs. f: OR = 1.151, 95% CI, 1.020–1.300). For the genotype analysis of VDR FokI, no statistical differences exist in the models of heterozygote comparison (Ff vs. ff), homozygote comparison (FF vs. ff) and dominant model (FF + Ff vs. ff) (p > 0.05). However, in recessive model (FF vs. Ff + ff), there is a significant association between VDR polymorphism and spinal diseases (OR = 1.209, 95% CI, 1.017–1.436). In subgroup analysis, the results show that allele F is a risk factor for spinal diseases in each estimation. In hospital-based subgroup, the significant differences exist in FF vs. ff and FF vs. Ff + FF models. In degenerative spine diseases group, the results are consistent with that of overall studies.ConclusionsAccording to results of this meta-analysis, allele F is associated with the increased risk of spinal diseases. FF genotype may contribute to the susceptibility of spinal diseases. Therefore, VDR FokI polymorphism is related with spinal diseases.

VDR Gene variation and insulin resistance related diseases

BackgroundVitamin D status may influence the risk of Insulin resistance related diseases such as Type 2 diabetes (T2DM), metabolic syndrome (MetS), and polycystic ovarian syndrome (PCOS). Several studies have assessed vitamin D receptor (VDR) gene polymorphism in relationship with these diseases; however, results remain inconsistent. Our study was conducted to elucidate whether VDR Gene polymorphisms could predict insulin resistance on a large scale.MethodsA meta-analysis using MEDLINE and EMBASE, was performed up to December 16th, 2016. Studies reporting association of vitamin D gene polymorphism with incident T2DM, MetS and PCOS outcomes were included and sub-group analysis by pigment of skin and latitude were performed.ResultsA total of 28 articles based on four gene variation, and comprising 9232 participants with 5193 Insulin resistance related diseases patients were included. No significant associations of the VDR ApaI, BsmI, FokI and TaqI variant with Insulin resistance related diseases were found. However, sub-group analysis analysis showed that PCOS in TaqI (OR = 1.47, 95% CI = 1.03–2.09, P = 0.03) for T allele and MetS for G allele (OR = 1.41, 95% CI = 1.07–1.85, P = 0.01) in BsmI was significant association with VDR gene polymorphism. Simultaneously, sub-group analysis showed VDR ApaI rs7975232(G > T)variant was associated with insulin resistance related diseases in Asians (GG/GT + TT) (OR, 1.62; 95% CI, 1.03–2.53; P = 0.04) and population who lived in middle latitude district (30–60°) (GG/GT + TT) (OR, 1.22; 95% CI, 1.04–1.43; P = 0.02), VDR BsmI rs1544410 (A > G)and VDR Taq1rs731236 (T/C) variant were associated with insulin resistance related diseases in Caucasian (dark-pigmented).ConclusionThe results suggested that the association between insulin resistance related diseases and VDR ApaI, BsmI, FokI variant was more obvious in dark-pigmented Caucasians and Asians but not in Caucasian with white skin.

Vitamin D receptor gene FokI polymorphism in Egyptian children and adolescents with SLE: A case-control study.

Background Childhood-onset systemic lupus erythematosus (cSLE) is a lifelong autoimmune disorder. The vitamin D receptor (VDR) gene is a potential candidate gene for cSLE susceptibility. In this study, we aimed to investigate the FokI polymorphism in the VDR gene in Egyptian children and adolescents with SLE, to determine whether this polymorphism could be a genetic marker for cSLE susceptibility or disease activity and we also measured the serum level of 25-hydroxyvitamin D [25(OH) D] to assess its relation to such polymorphism. Methods This was a case-control study, which included 300 patients with cSLE and 300 age, sex, and ethnicity-matched healthy controls. All participants were genotyped for the VDR gene FokI (rs2228570) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while the serum [25(OH) D] levels were measured by enzyme-linked immunosorbent assay (ELISA). Results The VDR FokI FF genotype and F allele were overrepresented among cSLE patients compared with the controls, [odds ratio (OR) = 2.7; 95% confidence interval (CI): 1.6-4.4 for the FF genotype; p = 0.000; and OR = 1.6; 95% CI: 1.27-2.05 for the F allele; p = 0.000, respectively]. We found a significant association between VDR FokI FF genotype with lupus nephritis (OR: 4.8; 95% CI: 2.2-10.6; p = 0.002); and high disease activity index score ( p = 0.01). Conclusions The FokI polymorphism in the VDR gene may contribute to susceptibility to SLE in Egyptian children and adolescents. Moreover, the FF genotype constituted a risk factor for the development of lupus nephritis and was associated with low serum [25(OH) D] levels as well as higher disease activity index score among studied patients with cSLE.

Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis

BackgroundThe association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial. MethodsThis meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity. ResultsA total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype. High latitude (40.1–50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1–30°N) people with ApaI homozygous genotype, ‘> 2013’ publication year people in the allele contrast and dominant models of FokI, ‘> 40 years’ age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk. ConclusionTaqI polymorphism is a significant protective factor for MS. However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.

The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children

BackgroundIn the present study, we explored the link between vitamin D receptor (VDR) BsmI, TaqI, ApaI and FokI gene polymorphisms with deciduous tooth decay in Chinese children.MethodsOur study included 380 Chinese children aged 4–7 years, whose DNA sample was collected from the buccal mucosa. VDR gene polymorphisms was determined by PCR-RFLP.ResultsThe adjusted logistic regression analysis demonstrated that BsmI containing the Bb genotype was linked with the increased risk of deciduous tooth decay (OR = 1.856, 95% CI = [1.184, 2.908], p = 0.007). However, VDR polymorphisms ApaI, TaqI and FokI were not associated with deciduous tooth decay (ApaI: OR = 0.839, 95% CI = [0.614, 1.145], p = 0.268; TaqI: OR = 1.150, 95% CI = [0.495, 2.672], p = 0.744; FokI: OR = 0.856, 95% CI = [0.616, 1.191], p = 0.356).ConclusionsOur results showed that VDR BsmI polymorphism was associated with the risk of deciduous tooth decay in Chinese children aged 4–7 years. However, the specific mechanism remains to further verify through experiment.

Abstract 1278: Effect modifications of vitamin D receptor common polymorphisms association with prostate cancer by serum vitamin D related behavioral and biological factors

Abstract Background: Several roles have been proposed for vitamin D and the vitamin D receptor (VDR) in prostate cancer (PCa) pathogenesis and progression. However, previous genetic epidemiologic studies have provided limited support linking VDR polymorphisms to PCa due to complexity of vitamin D metabolism and potential gene and environmental interactions. In this study, we investigated the association of VDR genotypes with PCa incidence and aggressiveness in African Americans (AAs) and European Americans (EAs) and if the associations were modified by behavioral and biological factors that influence serum vitamin D levels. Methods: The total of 810 AAs and 487 EAs from Chicago, IL and Washington, D.C. were included in this study. Seven single-nucleotide polymorphisms (SNPs) in and around the VDR gene and 105 ancestry informative markers were genotyped. We performed logistic regression analyses adjusting for relevant variables. Results: In EAs, TaqI (rs73136) and BsmI (rs1544410) minor alleles revealed a protective effect against PCa, while in AAs, FokI (rs2228570) was associated with overall PCa risk (OR=0.74, 95% C.I.: 0.57-0.96). The heterogeneous associations observed in our study could be due to difference in prevalence of vitamin D deficiency between AAs and EAS and effect modifications by behavioral and biological factors that affect serum vitamin D levels. Therefore, we investigated if behavioral and biological factors that influence serum vitamin D modified the associations between VDR polymorphisms and PCa, and we found evidence suggesting that these behavioral and biological factors modify the effect of VDR on PCa. In AAs, we observed statistically significant interaction between two VDR polymorphisms, FokI and TaqI, and vitamin D intake (PInteraction=0.01 and PInteraction=0.03 respectively). We also observed evidence of interactions between VDR gene variants and other behavioral and biological factors that lower serum vitamin D levels in both AAs and EAs. In AAs, calcium intake and skin pigmentation may modify the effects of VDR on PCa. In EAs, BMI may modify the effect of VDR. Conclusions: Although a larger sample size is necessary to confirm the observation, we demonstrated that vitamin D related behavioral and biological factors modify the effect of VDR genotypes on PCa. Impact: The VDR gene is involved in PCa pathogenesis and progression, and polymorphisms in VDR gene and vitamin D are likely to alter the function of the gene. Citation Format: Ken Batai, Adam B. Murphy, Ebony Shah, Chiledum Ahaghotu, Rick A. Kittles. Effect modifications of vitamin D receptor common polymorphisms association with prostate cancer by serum vitamin D related behavioral and biological factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1278. doi:10.1158/1538-7445.AM2017-1278

Expression of JAZF1, ABCC8, KCNJ11and Notch2 genes and vitamin D receptor polymorphisms in type 2 diabetes, and their association with microvascular complications.

We studied JAZF1, ABCC8, KCNJ11and Notch2 gene expression and vitamin D receptor (VDR) polymorphisms (Fok1 and Bsm1) in patients with type 2 diabetes mellitus (T2DM) and tried to find out their association with microvascular complications in these patients. The study was conducted on 180 patients (93 complicated and 87 noncomplicated) and 150 healthy subjects. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to assess gene expression and real-time PCR was used to detect VDR genotypes. Serum vitamin D was assessed using Elisa technique. After adjustment for age, sex, body mass index and glycated hemoglobin, altered Notch2 gene expression was found between patients and controls and between complicated and noncomplicated cases (p = 0.001 and 0.001, respectively) and ABCC8 gene expression showed significant difference between patients and controls only (p = 0.003), while JAZF1and KCNJ11 expression showed no significant difference between the studied groups (p = 0.3 and 0.4, respectively). Serum vitamin D level was decreased in patients compared with controls (p = 0.001), while no difference was detected between complicated and noncomplicated cases (p = 0.1). Our results revealed no significant difference in VDR Fok1 and Bsm1 genotype distributions (p = 0.7 and 0.1, respectively) and allele frequencies (p = 0.4 and 0.1, respectively) between patients and controls. Patients with complications showed increased frequencies of Fok1GG genotype and G allele, while patients without complications showed increased frequencies of AA, then AG Fok1 genotype and A allele (p = 0.001 and 0.001, respectively). In addition, the frequencies of CC Bsm1 genotype and C allele were significantly higher among patients with complications, while frequencies of TT Bsm1 genotype and T allele were significantly higher among patients without complications (p = 0.02 and 0.003, respectively). Altered expression of Notch2 and ABCC8 genes may play a role in the pathogenesis of T2DM. Altered expression of Notch2 and VDR polymorphisms may play a role in the development of microvascular complications in diabetic patients. These results may assist in early identification and management of diabetic complications.

Unveiling the association between Vitamin D Receptor and Poly Cystic Ovary Syndrome - a systematic review and meta-analysis.

Background: Low Vitamin D status observed in the populations globally and its associations with diverse systems have kindled the interest for Vitamin D in medical literature in last two decades. Accumulating evidence manifest that deficiency of Vitamin D might be a causal factor in the pathogenesis of various features of Poly Cystic Ovary Syndrome (PCOS). This notion is supported by the fact that > 3 % of the human genome is regulated by vitamin D receptor (VDR). Therefore, this meta-analysis was carried out to quantify the magnitude of risk associated with VDR polymorphisms (BsmI, TaqI, FokI and ApaI) and PCOS susceptibility. Methods: Pub-med, EMBASE, Cochrane database, Science direct, Scirus, ISI web of knowledge and Google scholar were searched for all years until July 2016. The case control studies related to VDR polymorphism and PCOS risk were selected according to inclusion and exclusion criteria. Nine studies of the initial 553 hits reporting VDR polymorphism in PCOS were included. All statistical analysis was performed using the STATA 11.0 software and odd ratio with 95 % confidence intervals was used as effect size to assess the strength of associations. Results: Nine studies comprising 1558 cases and 1033 controls were included in this meta-analysis. Significant association between VDR Fok1 polymorphisms and PCOS risk was observed. In further stratified analysis, an increased risks were observed among Asian and African populations for Taq1 polymorphism. Apa1 and Bsm1 polymorphism was found not to be a risk factor for PCOS susceptibility. Conclusion: The FokI polymorphism is found to be a significant risk factor for PCOS.

Vitamin D receptor gene polymorphisms association with the risk of sepsis and mortality.

Association of vitamin D receptor (VDR) gene polymorphisms with sepsis risk and mortality was studied. VDR FokI CC genotype was associated with increased sepsis risk (OR=13.396, p=.000009) compared to the TT genotype. Results suggest possible role of VDR FokI (rs2228570) as a molecular biomarker of increased sepsis risk.

Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus

At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60±11.59years and 48.21±12.17years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p=0.011) and LDL-cholesterol (p=0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p=0.031) and the TT genotype was associated with lower LDL-cholesterol level (p=0.007). The frequency of AAT and GGC haplotypes was also different between groups (p=0.014; p=0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.

Vitamin D receptor polymorphisms and related biochemical parameters in various cancer species

Abstract Objective Certain cancer types have been shown to be associated with vitamin D deficiency. The aim of this study was to appraise the relationship between the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) of VDR Fok1 and Bsm1 with serum vitamin D, calcium and phosphorus levels among patients of lung, colon, breast and pancreatic cancer patients. Materials and methods Groups; lung, colon, breast and pancreatic cancer patients (n=212) and 58 age-matched healthy controls. Serum levels of vitamin D were measured by immunochemiluminesence method and Fok1 and Bsm1 genotypes were assessed with Real-Time Polymerase Chain Reaction. Results VDR Fok1 and Bsm1 genetic polymorphisms have a significant difference between lung cancer and control group subjects (p=0.042, p=0.040, respectively). VDR Bsm1 genetic polymorphism has a significant association between breast cancer and control group according to the logistic regression model (p=0.038). Vitamin D levels were found significantly lower in all cancer groups (p&lt;0.01). Phosphorus levels of lung cancer and calcium levels of pancreatic cancer patients were statistically significantly lower than control group (p&lt;0.02, p&lt;0.01). Conclusion This study indicates that VDR genetic polymorphisms, calcium, phosphorus and vitamin D status of individuals were associated with certain cancer species.

Vitamin D receptor polymorphisms or serum levels as key drivers of breast cancer development? The question of the vitamin D pathway

As total vitamin D levels are often lower in black than in white Americans, the former are frequently classified as vitamin D-deficient. To fully understand African vitamin D (25(OH)D) status, other factors should be considered, e.g. vitamin D blood carrier, vitamin D-binding protein (DBP), vitamin D receptor (VDR) and DBP polymorphisms. A prospective study on an indigenous black Tanzanian and a Caucasian Italian population was performed on 50 healthy donors from both populations and 35 Caucasian and 18 African breast cancer patients. 25(OH)D and DBP serum levels were analyzed by ELISA. A1012G, Cdx2 and Fok1 VDR polymorphisms and DBP polymorphisms rs4588 and rs7041 were genotyped by real-time PCR. Vitamin D and DBP levels were lower in healthy African donors than in Caucasians. Africans had a significantly higher frequency of AA and CC for Cdx2 and Fok1 polymorphisms, respectively. These allelic variants were related to a higher transcription of VDR gene and a higher activity of VDR receptor. With regard to polymorphism distribution, Africans showed innate higher levels and activity of VDR. We conclude that a strengthening of the vitamin D pathway could have a protective role against the development of breast cancer in the African population.

Vitamin D receptor gene polymorphisms in children with kidney stone disease.

Subaşı B, Gökçe İ, Delil K, Alpay H. Vitamin D receptor gene polymorphisms in children with kidney stone disease. Turk J Pediatr 2017; 59: 404-409. Kidney stone disease has a multifactorial etiology involving the interaction of genetic and environmental factors. There is an increased risk of stone formation in the relatives of idiopathic stone patients, which can be explained up to 60% by genetic factors. This study was conducted to explore the association of vitamin D receptor (VDR) gene polymorphisms with the risk of urolithiasis (UL) in Turkish children. We investigated the VDR gene polymorphisms: ApaI, BsmI, TagI, Cdx2, FokI, in 52 children (26 boys, 26 girls) with UL and in 51 healthy children (22 boys, 29 girls) without UL. Apa I, BsmI, TagI, Cdx2, FokI genotypes were analyzed by Apa I, BsmI, TagI, Cdx2, FokI restriction enzyme digestion, respectively. The resulting alleles are designated as ABTCF (ApaI, BsmI, TagI, Cdx2, and FokI restriction site is absent), or abtcf (ApaI, BsmI, TagI, Cdx2, FokI restriction site is present), respectively. Genotype and allele frequencies were calculated, and the association with UL, hypercalciuria and hypocitraturia was investigated. Our data provide no statistically significant evidence for an association between UL and VDR ApaI, BsmI, TagI, Cdx2, and FokI genotype and allele frequencies. Patients with hypocitraturia and hypercalciuria were compared with the control group and no statistically significant difference was detected in terms of VDR gene ApaI, BsmI, TagI, Cdx2, and FokI polymorphisms and allele frequencies. Our data suggest that the VDR ApaI, BsmI, TagI, Cdx2, and FokI polymorphisms do not indicate a significant risk for UL.

Vitamin D Status and its Receptor Genes BsmI, FokI, ApaI, TaqI Polymorphism in Relation to Glucose Metabolism in Obese Iraqi Type 2 Diabetes Mellitus Patients

Background: Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 2 diabetes mellitus (T2DM). However, the data to date have been inconclusive. Previous studies have suggested an influence of vitamin D receptor alleles on glucose metabolism and on susceptibility to type 2 diabetes mellitus in different ethnic populations through the action of vitamin D endocrine system which related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes. To investigate the relationship between a single nucleotide polymorphism (SNP) of VDR gene and T2DM more studies had been done. However, different results have been found in different spots of the world. Therefore, more studies are needed to understand the variation in these results. This is the first study that shows the implication of the SNP of VDR gene in T2DM in Iraqi patients. Objective: To assess the correlation between serum 25(OH)D3 levels, and vitamin D receptor (VDR) polymorphisms (Fok1, BsmI, TaqI and ApaI), and glycemic control in obese T2DM Iraqi population, this study was performed. Materials and methods: 200 clinically diagnosed T2DM patients, distributed into three subgroups according to therapeutic pattern and 75 healthy controls from the Iraqi population were recruited in this study. The association between the VDR gene SNPs and the T2DM was determined using Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, and genotype and allele frequencies were calculated between the T2DM and control groups. Results: No significant differences between mean age and the body mass index between both case and control groups were observed. According to current glycemic control consensus, results demonstrated only 20.5 percent of the T2DM patients met this target, which meant that 79.5 percent of the cases were suffering from poor glycemic control 25(OH)D3 levels were significantly lower in the T2DM patients than in the control group, being 17.49 ± 1.12 ng/ml and 31.26 ± 1.25 ng/ml, in the patient and control groups, respectively (p 20 < 30 ng/ml (chi-squared test, p<0.0001). The gene polymorphism analysis for T2DM showed that genotype and alleles frequencies for the VDR genes were in agreement with Hardy–Weinberg equilibrium in all cases. Conclusion: VDR gene polymorphism analysis revealed that neither genotypes nor alleles of VDR BsmI, ApaI showed a significant variation between T2DM patients and controls. In contrast‚ the FF genotype of VDR FokI and TT genotype of VDR TaqI showed a significant (P<0.0001) increase in T2DM patients in comparison to controls. FF and TT homozygotes had significantly higher baseline fasting glucose and HOMI-IR levels than f allele carriers. In addition, data found significantly elevated interlukin IL-6, TNF-α, IL -1β and decreased osteocalcin in association with the Taq1 polymorphism.

Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients

IntroductionThe vitamin D receptor (VDR) gene is a candidate for susceptibility to autoimmune disorders. Aim of the workTo study the frequency of vitamin D deficiency in Egyptian systemic lupus erythematosus (SLE) patients and investigate the association of BsmI and FokI VDR gene polymorphisms with disease susceptibility, activity and damage. Patients and methodsForty-five SLE patients and 40 controls were enrolled. SLE Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) damage index were assessed for the patients. Serum vitamin D levels were measured in all subjects. Genotyping for the VDR BsmI and FokI gene polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism for only 34 patients and 16 controls. ResultsThe mean age of SLE patients was 28.8±7.9years and disease duration 11.3±9.8years. Vitamin D level was significantly lower in patients than control (p<0.001) and significantly correlated with C3 and C4 levels (p<0.001) and inversely with SLEDAI (p<0.001), SLICC (p=0.005), anti-ds DNA (p<0.001) and ESR (p=0.011). There were no significant differences in genotype and allelic frequencies of FokI and BsmI polymorphisms between patients and controls. There was a significant relation of FokI polymorphisms with serum vitamin D level (p=0.002), SLEDAI (p=0.021) and SLICC (p=0.002). BsmI polymorphisms showed significant associations with neuropsychiatric damage, low complement, fever and mucosal ulcers. ConclusionsVDR FokI polymorphism in SLE patients is significantly related to low vitamin D level in SLE patients and both are associated with increasing disease activity and damage denoting important implications in this disease.