Growing evidence suggests an elevated risk for colorectal neoplasia among individuals with low levels of vitamin D, the biological actions of which are mediated by the vitamin D receptor (VDR). To investigate the association among vitamin D status, VDR polymorphisms (FokI, and BsmI), and colorectal adenoma, we conducted a meta-analysis of nine studies of circulating levels of 25-hydroxyvitamin D (25(OH)D) and five studies of FokI or BsmI polymorphisms in relation to colorectal adenomas. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model. A total of 3398 colorectal adenomas for 25(OH)D and 1754 colorectal adenomas for VDR were included in the meta-analysis. We identified a significant inverse association between colorectal adenoma (combined RR, 0.93; 95% CI, 0.87-0.98 per 10 ng/mL increase in 25(OH)D levels). When we examined FokI and BsmI polymorphisms in the meta-analysis, we found no association for either FokI (combined RR, 1.00; 95% CI, 0.95-1.06) or BsmI (combined RR, 0.99; 95% CI, 0.93-1.05) in the additive model. These data suggest an inverse association between circulating 25(OH)D levels and colorectal adenoma risk.
Adenoma ; Receptors, Calcitriol ; Vitamin D ; Vitamins

Humans ; Rural Population ; Hyperglycemia/genetics* ; Receptors, Calcitriol/genetics*

Humans ; Polymorphism, Genetic ; Receptors, Calcitriol ; genetics ; Rickets ; genetics

Breast cancer is the leading cause of cancer death among women around the world and its incidence is annually increasing. The vitamin D receptor (VDR) gene is a member of the nuclear receptor superfamily, which is expressed in breast tissue and known to modulate the rate of cell proliferation. Association between the VDR gene polymorphisms and cancer development has been suggested by several studies. However, the relationship between VDR polymorphisms and breast cancer is controversial and has not been confirmed by all studies. The purpose of this study was to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polymorphisms with breast cancer in Turkish patients. In this study, 78 patients with breast cancer and 27 healthy individuals were enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients with breast cancer was similar to that in the normal population. Our data indicate that no significant differences exist between the patients and control subjects.
Breast Neoplasms/*genetics ; Gene Frequency ; Genotype ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic/*genetics ; Receptors, Calcitriol/*genetics

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.
DNA Restriction Enzymes ; Genotype ; Humans ; Macrophages ; Prevalence ; Receptors, Calcitriol ; Tuberculosis ; Vitamin D ; Vitamins

BACKGROUND: The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis. METHODS: We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers. RESULTS: The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI). CONCLUSION: Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.
DNA Restriction Enzymes ; Genotype ; Humans ; Macrophages ; Prevalence ; Receptors, Calcitriol ; Tuberculosis ; Vitamin D ; Vitamins

Vitamin D plays an important role in mineral and bone homeostasis, immune responses, cardiovascular function and keratinocyte proliferation and differentiation. Vitamin D performs most of its functions by binding to vitamin D receptors (VDR), which interact with other intracellular signaling pathways to regulate bone metabolism, inflammation, immunity, cell cycle progression and apoptosis. Autophagy is a basic stress response in yeast, plants and mammals, and plays a critical role in maintaining optimal functional states at the level of cells and organs. Vitamin D/VDR plays an anti-infection role via inducing and regulating autophagy.
Animals ; Autophagy ; Humans ; Inflammation ; Mammals/metabolism* ; Receptors, Calcitriol/metabolism* ; Vitamin D/physiology* ; Vitamins

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

Objective: To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and gestational diabetes mellitus (GDM) and provide evidence for the study of the mechanism of GDM. Methods: A case-control study design was used to study pregnant women who delivered in the obstetrics department of the First Hospital of Shanxi Medical University from March 1, 2012 to July 30, 2014. Of these, 334 cases were diagnosed with GDM and were matched 1∶1 by age, gestation time and residence to corresponding healthy controls. DNA genotyping was performed for the study subjects, and those with genotyping deletions >10% were excluded. Finally 323 cases and 320 controls were included in the study. Under co-dominant, dominant, recessive, and allele genetic models, unconditional logistic regression analysis on the relationship between VDR gene locus polymorphism and GDM was conducted. And software Haploview was used to analyze the relationship between haplotype and GDM. Results: At the genetic level, VDR gene was associated with the risk of developing GDM (P<0.05). After adjusting for pre-pregnancy body mass index, family history of diabetes, it was found that rs7967152 loci was associated with an increased risk of developing GDM (AC vs. AA, OR=1.58, 95%CI: 1.13-2.21; AC+CC vs. AA, OR=1.58, 95%CI: 1.15-2.18; C vs. A, OR=1.41, 95%CI: 1.10-1.82) and rs2238140 loci was associated with an increased risk of developing GDM (AA vs. GG, OR=2.24, 95%CI: 1.19-4.20; GA+AA vs. GG, OR=1.48, 95%CI: 1.07-2.03; A vs. G, OR=1.43, 95%CI: 1.11-1.83). Carrying rs2853564 locus AG genotype and AG+GG genotype (OR=1.46, 95%CI: 1.04-2.05; OR=1.45, 95%CI: 1.05-2.00) compared with carrying AA genotype and carrying rs2853566 locus AG genotype and AG+GG genotype (OR=1.43, 95%CI: 1.03-2.00; OR=1.41, 95%CI: 1.02-1.94) compared with carrying AA genotype were risk factors for GDM. Haplotype block consisting of rs1544410, rs7967152 in the VDR gene with GC haplotype was a risk factor for GDM(OR=1.50, 95%CI: 1.15-1.97). Conclusions: VDR gene rs7967152, rs2238140, rs2853564, rs2853566 locus polymorphisms and block (rs1544410, rs7967152) GC haplotype were associated with an incrased risk of developing GDM.
Case-Control Studies ; Diabetes, Gestational/genetics* ; Female ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Pregnancy ; Receptors, Calcitriol/genetics*

BACKGROUND: Rosacea is a chronic inflammatory disease characterized by centrofacial erythema. Excess cathelicidin is suggested to be important to the pathophysiology of the disease. Recently, presence of a vitamin D response element was revealed in the cathelicidin gene promoter. OBJECTIVE: The aim of this study was to determine whether vitamin D and cathelicidin are associated with rosacea, both serologically and histopathologically. METHODS: Subjects with rosacea and without chronic skin disorders were enrolled in the patient and control groups, respectively. Serum 25-hydroxy-vitamin D and cathelicidin levels were measured. Tissue expression of cathelicidin and vitamin D receptor were measured with immunostaining-intensity-distribution index. RESULTS: The mean serum 25-hydroxyvitamin D level of patients with rosacea was 12.18±5.65 ng/ml, which is lower than that of the controls (17.41±6.75 ng/ml). Mean serum cathelicidin levels in patients with rosacea and the controls were 85.0±26.1 ng/ml and 55.0±23.3 ng/ml, respectively. Cathelicidin expression in rosacea tissue was significantly higher than that in control tissue (5.21 vs. 4.03). No significant difference was observed in vitamin D receptor expression. CONCLUSION: Higher cathelicidin expression in rosacea supports the hypothesis that an abnormal inflammatory response of the innate immune system is important in pathogenesis of rosacea, but the role of high cathelicidin serum levels is complicated. Serum vitamin D was lower in patients with rosacea, although serum cathelicidin was higher than that of the controls. This suggests that the role of vitamin D level in the pathogenesis of rosacea merits further investigation.
Erythema ; Humans ; Immune System ; Receptors, Calcitriol ; Rosacea* ; Skin ; Vitamin D Response Element ; Vitamin D* ; Vitamins*