AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were stu...AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide gene polymorphisms of the VDR were investigatedby polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was signif icantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was signif i-cantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively).CONCLUSION: VDR genetic polymorphisms are sig-nificantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology.展开更多
Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic mel...Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.展开更多
The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing ...The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor(VDR), we examined their response to different concentrations of 25-hydroxy vitamin D_3[25(OH)D_3](100 or 500 nmol·L^(-1)) and 1,25-dihydroxy vitamin D_3[1,25(OH)_2D_3](0.1 or 0.5 nmol·L^(-1)) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand(RANKL) and macrophage colony-stimulating factor(M-CSF). Tartrate-resistant acid phosphatase(TRAP)histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue(ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting.Quantitative reverse transcription-PCR(q RT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by q RT-PCR, was stimulated in response to 500 nmol·L^(-1)of 25(OH)D_3and 0.1–0.5 nmol·L^(-1)of 1,25(OH)_2D_3,upregulating cytochrome P450 family 27 subfamily B member 1(CYP27B1) and cytochrome P450 family 24 subfamily A member 1(CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4(tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1(nfatc1) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D_3and1,25(OH)_2D_3reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)_2D_3on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.展开更多
Nonalcoholic steatohepatitis(NASH)is a progressed stage of non-alcoholic fatty liver disease,and available therapeutic strategies for NASH are limited.Vitamin D receptor(VDR)is proposed as a druggable target for NASH ...Nonalcoholic steatohepatitis(NASH)is a progressed stage of non-alcoholic fatty liver disease,and available therapeutic strategies for NASH are limited.Vitamin D receptor(VDR)is proposed as a druggable target for NASH due to the discovery of vitamin D deficiency in NASH patients.To date,vitamin D supplementation has not consistently conferred expected therapeutic benefits,raising the question of whether VDR can serve as a proper drug target for NASH.It is known that VDR can interact with other ligands such as bile acids in addition to vitamin D,and its expression can be induced by fatty acids,and insulin.It has also been shown that while activation of VDR in hepatic macrophages and hepatic stellate cells resulted in attenuation of hepatic inflammation and fibrosis,activation of VDR in hepatocytes could accelerate lipid accumulation.Thus,the multiplicity of VDR ligands,together with the cell type-specificity of VDR activation,must be taken into consideration in assessing the validity of VDR being a potential druggable target for NASH treatment.To this end,we have evaluated the relationship between VDR activation and various contributing factors,such as gut microbiota,bile acid,fatty acids,and insulin,in addition to vitamin D,with an expectation that a potential drug might be identified that can elicit VDR activation in a tissue-and/or cell type-specific manner and therefore achieving therapeutic benefits in NASH.展开更多
Objective To explore the association of single nucleotide polymorphisms(SNPs)of the vitamin D receptor gene(VDR)with circulating lipids considering gender differences.Methods Of the Han Chinese adults recruited from a...Objective To explore the association of single nucleotide polymorphisms(SNPs)of the vitamin D receptor gene(VDR)with circulating lipids considering gender differences.Methods Of the Han Chinese adults recruited from a health examination center for inclusion in the study,the circulating lipids,25-hydroxyvitamin D(25OHD),and other parameters were measured.The VDR SNPs of Cdx2(rs11568820),Fok1(rs2228570),Apa1(rs7975232),and Taq1(rs731236)were genotyped with a qPCR test using blood DNA samples,and their associations with lipids were analyzed using logistic regression.Results In the female participants(n=236 with dyslipidemia and 888 without dyslipidemia),multiple genotype models of Fok1 indicated a positive correlation of B(not A)alleles with LDLC level(P<0.05).In the male participants(n=299 with dyslipidemia and 564 without dyslipidemia),the recessive model of Cdx2 and the additive and recessive models of Fok1 differed(P<0.05)between the HDLC-classified subgroups,respectively,and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC(P<0.05).Conclusion In the Chinese Han adults included in the study,the Fok1 B-allele of VDR was associated with higher LDLC in females,and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males.The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.展开更多
BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unkno...BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.展开更多
<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for in...<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.展开更多
AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of ...AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.展开更多
AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10)...AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P < 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P < 0.01) and from IBD patients(0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P < 0.05) and from IBD patients with Crohn's disease(r =-0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P < 0.05) and with patient age(r = 0.54, P < 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.展开更多
Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han p...Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI. Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.展开更多
Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by ...Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.展开更多
Aim: To investigate the single nucleotide polymorphism of vitamin D receptor (VDR) gene start codon in the Han nationality in Hubei and its relationship to the susceptibility to prostate cancel (PCa). Methods: The VDR...Aim: To investigate the single nucleotide polymorphism of vitamin D receptor (VDR) gene start codon in the Han nationality in Hubei and its relationship to the susceptibility to prostate cancel (PCa). Methods: The VDR genotypes were determined by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 80 patients with PCa and 96 normal male controls from the Han nationality in Hubei, using endonuclease Fok. Direct sequencing was done in part of the PCR products. Results: The frequency distribution of Fok I alleles in this cohort all followed the Hardy-Weinberg equilibrium. The distribution of genotypes and alleles had no significant difference between PCa patients and the controls (P>0.05). Conclusion: There was no significant relationship between Fok I polymorphism of VDR gene start codon and PCa in the Han nationality in Hubei.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for the...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for these reasons,it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment.The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled;consequently,at moment there are not effective treatments.In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis,to the vitamin D/vitamin D receptor(VD/VDR)axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD.However,the data currently available,including clinical trials with VD supplementation,still provides a contrasting picture.The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR.Based on recent data from literature,we focused in particular on the hypothesis that VDR itself,independently from its traditional ligand VD,may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.展开更多
Background:The vitamin D receptor(VDR) gene is a primary candidate gene for tuberculosis susceptibility,but results of previous studies are somewhat contradictory and underpowered.Thus,it is essential to further explo...Background:The vitamin D receptor(VDR) gene is a primary candidate gene for tuberculosis susceptibility,but results of previous studies are somewhat contradictory and underpowered.Thus,it is essential to further explore the association between VDR gene polymorphisms and risk of pulmonary tuberculosis(PTB).Methods:A systematic review and meta-analysis about the association between FokI,TaqI,ApaI and BsmI polymorphisms and PTB susceptibility was conducted.Statistical Package for Social Science(Version 13.0) and Review Manager(Version 4.2,The Cochrane Collaboration) were used to analyze the data reported in studies.Results:A total of 13 studies with 2 262 cases and 2 833 controls were involved in the FokI polymorphism,and the results showed FokI polymorphism was associated with PTB susceptibility(allele f vs F:OR=1.12,95% CI=[1.02,1.23];the additive effect model ff vs FF:OR=1.40,95%CI=[1.10,1.77];the recessive genetic model ff vs Ff+FF:OR=1.39,95%CI=[1.12,1.71]).No significant associations were observed between TaqI(15 studies with 3 031 cases and 3 132 controls),ApaI(7 studies with 1 495 cases and 1 922 controls),BsmI(6 studies with 919 cases and 1 250 controls) variants and PTB susceptibility.Conclusion:We found variant FokI polymorphism of VDR gene may play a risky role in PTB development,and the genetic model was presumed to be recessive.展开更多
AIM: To observe the expression of vitamin D receptor(VDR) in human specimen and immortalized human corneal epithelium cells(HCEC) when challenged with fusarium solani. Moreover, we decided to discover the pathway of V...AIM: To observe the expression of vitamin D receptor(VDR) in human specimen and immortalized human corneal epithelium cells(HCEC) when challenged with fusarium solani. Moreover, we decided to discover the pathway of VDR expression. Also, we would like to detect the expression of cathelicidin antimicrobial peptide(CAMP) in the downstream pathway of VDR.·METHODS: Immunohistochemistry was used to examine the VDR expression in HCEC from healthy and fungal keratitis patients. Real time quantitative polymerase chain reaction(qPCR) was performed to observe the messenger ribonucleic acid(mRNA) change of VDR when immortalized HCEC were challenged with fusarium solani for different hours. CAMP was detected at both m RNA and protein levels.·RESULTS: We found out that the VDR expression in fusarium solani keratitis patients' specimen was much more than that in healthy people. The m RNA and protein expression of VDR increased when we stimulated HCEC with fusarium solani antigen(P <0.01) and it could be inhibited by toll like receptor 2(TLR2) monoclonal antibody. The CAMP expression was decreased because of fusarium solani antigen stimulation(P <0.01).·CONCLUSION: The VDR expression can be increased via TLR2/1-VDR pathway while the CAMP expression is decreased by the stimulation of fusarium solani antigen.展开更多
To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients wh...To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene’s promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.展开更多
Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3...Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.展开更多
Colorectal cancer represents the third cancer worldwide. Studies showed thatinsufficient levels of vitamin D may result in colorectal cancer. Genetic variations in genes controlling vitamin D activity would play a rol...Colorectal cancer represents the third cancer worldwide. Studies showed thatinsufficient levels of vitamin D may result in colorectal cancer. Genetic variations in genes controlling vitamin D activity would play a role in determining susceptibility to colorectal cancer. Aim of the work: to study the different genotypes of VDR polymorphisms and detect the association between serum levels of 25(OH)VitD and 1,25(OH)2VitD among sample of Egyptian patients with different stages of colorectal cancer. Methods: Ninety patients (60 with different stages of colorectal cancer and 30 patients with benign pathology of the colon) together with 30 healthy controls were examined using PCR-RFLP analysis for FokI, ApaI and TaqI polymorphisms. Results: Genotype distribution for ApaI polymorphism showed no statistically significant difference between patients (colorectal cancer and benign) and controls with p = 0.1. There was no statistically significant difference in FokI polymorphism where p = 0.26 and genotype distribution for TaqI was also insignificant with p = 0.016. The median serum level of 25(OH)VitD was low in cancer cases compared to the control group and benign cases with (p 0.001). There was no statisticallysignificant difference of median serum level of 1,25(OH)2VitD between benign and cancer cases. There was statistically significant difference of median serum level of 25(OH)VitD and 1,25(OH)2VitD between stage I and stage II with (p = 0.004) and (p 0.001), and between stage I and stage III with (p = 0.001)and (p 0.001), but no statistically significant difference between stage II and III with (p = 0.514). Conclusions: There is ethnic variability in vitamin D receptor gene polymorphisms. The lack of significant association of the studied gene polymorphism in our population suggests that its association with other functionally known gene polymorphism might have a role in the pathogenesis of colorectal cancer.展开更多
基金Supported by Grants from the Ricerca Sanitaria Finalizzata Program, Regione Piemonte, Italy
文摘AIM: To assess the relationship between vitamin D re-ceptor (VDR) gene polymorphisms and the presence of hepatocellular carcinoma (HCC). METHODS: Two-hundred forty patients who underwent liver transplantation were studied. The etiologies of liver disease were hepatitis C (100 patients), hepatitis B (37) and alcoholic liver disease (103). A group of 236 healthy subjects served as controls. HCC in the explanted liver was detected in 80 patients. The following single nucle-otide gene polymorphisms of the VDR were investigatedby polymerase chain reaction and restriction fragment length polymorphism: FokI C>T (F/f), BsmI A>G (B/b), ApaI T>G (A/a) and TaqI T>C (T/t) (BAT). RESULTS: The frequencies of genotypes in patients without and with HCC were for FokI F/F = 69, F/f = 73, f/f = 18 and F/F = 36, F/f = 36, f/f = 8; BsmI b/b = 45, B/b = 87, B/B = 28 and b/b = 33, B/b = 35, B/B = 12; for ApaI A/A = 53, A/a = 85, a/a = 22 and A/A = 27, A/a = 38, a/a = 15; for TaqI T/T = 44, T/t = 88, t/t = 28 and T/T = 32, T/t = 38, t/t = 10. Carriage of the b/b genotype of BsmI and the T/T genotype of TaqI was signif icantly associated with HCC (45/160 vs 33/80, P < 0.05 and 44/160 vs 32/80, P < 0.05, respectively). The absence of the A-T-C protective allele of BAT was signif i-cantly associated with the presence of HCC (46/80 vs 68/160, P < 0.05). A strong association was observed between carriage of the BAT A-T-C and G-T-T haplotypes and HCC only in alcoholic liver disease (7/46 vs 12/36 vs 11/21, P < 0.002, respectively).CONCLUSION: VDR genetic polymorphisms are sig-nificantly associated with the occurrence of HCC in patients with liver cirrhosis. This relationship is more specific for patients with an alcoholic etiology.
文摘Objective:To investigate whether vitamin D receptor gene(VDR)Bsm I-rs1544410 and Fok I-rs2228570 polymorphisms,smoking duration,and body mass index(BMI)are risk factors for cutaneous melanoma,especially metastatic melanoma.Methods:We studied 120 cutaneous melanoma cases[68 stage I and II non-metastatic melanoma(NMet M)patients,plus 52Stage III and IV metastatic melanoma(Met M)patients],and 120 matching healthy controls from northeast Italy.VDR polymorphisms were measured by restriction fragment length polymorphism analysis.Absence or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"respectively.Results:VDR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=3.18.Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk:≥20 years of smoking(OR=2.43);≥20 years of smoking combined with bb(OR=4.78),Bb+bb(OR=2.30),Ff(OR=3.04),and Ff+ff(OR=3.08);obesity(BMI>30Conclusions:Risk factors for cutaneous Met M include two VDR polymorphisms combined with smoking duration and obesity.Results suggest gene-environment implications in melanoma susceptibility and severity.Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.
基金financial support from Orthopaedic Research UK (P 470)Arthritis Research UK (grant 20299 and Oxford EOTC)
文摘The effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor(VDR), we examined their response to different concentrations of 25-hydroxy vitamin D_3[25(OH)D_3](100 or 500 nmol·L^(-1)) and 1,25-dihydroxy vitamin D_3[1,25(OH)_2D_3](0.1 or 0.5 nmol·L^(-1)) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand(RANKL) and macrophage colony-stimulating factor(M-CSF). Tartrate-resistant acid phosphatase(TRAP)histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue(ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting.Quantitative reverse transcription-PCR(q RT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by q RT-PCR, was stimulated in response to 500 nmol·L^(-1)of 25(OH)D_3and 0.1–0.5 nmol·L^(-1)of 1,25(OH)_2D_3,upregulating cytochrome P450 family 27 subfamily B member 1(CYP27B1) and cytochrome P450 family 24 subfamily A member 1(CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4(tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1(nfatc1) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D_3and1,25(OH)_2D_3reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)_2D_3on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.
基金Supported by the National Natural Science Foundation of China,No.81774084 and 81804020and Young Talent Promotion Project of Chinese Medicine Association,No.2019-QNRC2-C04.
文摘Nonalcoholic steatohepatitis(NASH)is a progressed stage of non-alcoholic fatty liver disease,and available therapeutic strategies for NASH are limited.Vitamin D receptor(VDR)is proposed as a druggable target for NASH due to the discovery of vitamin D deficiency in NASH patients.To date,vitamin D supplementation has not consistently conferred expected therapeutic benefits,raising the question of whether VDR can serve as a proper drug target for NASH.It is known that VDR can interact with other ligands such as bile acids in addition to vitamin D,and its expression can be induced by fatty acids,and insulin.It has also been shown that while activation of VDR in hepatic macrophages and hepatic stellate cells resulted in attenuation of hepatic inflammation and fibrosis,activation of VDR in hepatocytes could accelerate lipid accumulation.Thus,the multiplicity of VDR ligands,together with the cell type-specificity of VDR activation,must be taken into consideration in assessing the validity of VDR being a potential druggable target for NASH treatment.To this end,we have evaluated the relationship between VDR activation and various contributing factors,such as gut microbiota,bile acid,fatty acids,and insulin,in addition to vitamin D,with an expectation that a potential drug might be identified that can elicit VDR activation in a tissue-and/or cell type-specific manner and therefore achieving therapeutic benefits in NASH.
基金supported by the National Natural Science Foundation of China[grant number 81973038]Science,Technology and Innovation Commission of Shenzhen Municipality,China[grant number JCYJ20200109142446804].
文摘Objective To explore the association of single nucleotide polymorphisms(SNPs)of the vitamin D receptor gene(VDR)with circulating lipids considering gender differences.Methods Of the Han Chinese adults recruited from a health examination center for inclusion in the study,the circulating lipids,25-hydroxyvitamin D(25OHD),and other parameters were measured.The VDR SNPs of Cdx2(rs11568820),Fok1(rs2228570),Apa1(rs7975232),and Taq1(rs731236)were genotyped with a qPCR test using blood DNA samples,and their associations with lipids were analyzed using logistic regression.Results In the female participants(n=236 with dyslipidemia and 888 without dyslipidemia),multiple genotype models of Fok1 indicated a positive correlation of B(not A)alleles with LDLC level(P<0.05).In the male participants(n=299 with dyslipidemia and 564 without dyslipidemia),the recessive model of Cdx2 and the additive and recessive models of Fok1 differed(P<0.05)between the HDLC-classified subgroups,respectively,and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC(P<0.05).Conclusion In the Chinese Han adults included in the study,the Fok1 B-allele of VDR was associated with higher LDLC in females,and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males.The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.
基金Supported by The Key Projects of Natural Science Research of Anhui Province in China,No.201904a07020043.
文摘BACKGROUND The expression of jumonji domain-containing 3(Jmjd3)and trimethylated H3 lysine 27(H3K27me3)in active ulcerative colitis(UC)and the correlation between vitamin D receptor(VDR)and the Jmjd3 pathway are unknown.AIM To study the relationship between VDR,Jmjd3 and H3K27me3 in patients with active UC.METHODS One hundred patients with active UC and 56 healthy controls were enrolled in this study.The patients with active UC were divided into groups according to mild(n=29),moderate(n=32)and severe(n=29)disease activity based on the modified Mayo score.Vitamin D levels were measured by radioimmunoassay.Colonic mucosal tissues from UC patients and controls were collected by colonoscopy.The expression of VDR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry staining.RESULTS Patients with active UC had lower levels of serum vitamin D(13.7±2.8 ng/mL,P<0.001)than the controls(16.2±2.5 ng/mL).In the UC cohort,serum vitamin D level was negatively correlated with disease activity(r=-0.323,P=0.001).VDR expression in the mucosa of UC patients was reduced compared to that in normal tissues(P<0.001)and negatively correlated with disease activity(r=-0.868,P<0.001).Similar results for VDR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(P<0.05).Simultaneously,Jmjd3 expression significantly increased in UC patients(P<0.001),but no difference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(P<0.001),but up-regulated in the mild disease activity group in comparison with the moderate disease activity group of UC patients(P<0.05).Jmjd3 Level was negatively correlated with the level of VDR(r=-0.342,P=0.002)and H3K27me3(r=-0.341,P=0.002),while VDR level was positively correlated with H3K27me3(r=0.473,P<0.001).CONCLUSION Serum vitamin D and VDR were inversely correlated with disease activity in active UC.Jmjd3 expression increased in the colonic mucosa of active UC patients and was negatively associated with VDR and H3K27me3 level.
文摘<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.
基金Supported by Zhejiang provincial top key discipline in surgery
文摘AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.
基金Supported by National Institutes of Health GrantsNo.R25GM082406(to Isidro RA)+4 种基金U54CA163071 to Appleyard CBthe Office of Research from the Ponce Research Institute at Ponce Health Sciences UniversityWilliam Townsend Porter Predoctoral Fellowship from the American Physiological Society(to Isidro RA)the PHSU Molecular and Genomics Core Laboratory,RCMI Grant No.RR003050/MD007579the Puerto Rico Clinical and Translational Research Consortium,National Institutes of Health Grant U54MD007587(to Abreu Y,Medero P and Torres EA)
文摘AIM: To determine serum vitamin D levels and colonic vitamin D receptor(VDR) expression in inflammatory bowel disease(IBD) and non-IBD patients and correlate these with histopathology.METHODS: Puerto Rican IBD(n = 10) and non-IBD(n = 10) patients ≥ 21 years old scheduled for colonoscopy were recruited. Each patient completed a questionnaire and provided a serum sample and a colonic biopsy of normal-appearing mucosa. For IBD patients, an additional biopsy was collected from visually diseased mucosa. Serum vitamin D levels were measured by ultra-performance liquid chromatography and mass spectrometry. Hematoxylin and eosin stained tissue sections from colonic biopsies were classified histologically as normal or colitis(active/inactive), and scored for the degree of inflammation present(0-3, inactive/absent to severe). Tissue sections from colonic biopsies were also stained by immunohistochemistry for VDR, for which representative diagnostic areas were photographed and scored for staining intensity using a 4-point scale.RESULTS: The IBD cohort was significantly younger(40.40 ± 5.27, P < 0.05) than the non-IBD cohort(56.70 ± 1.64) with a higher prevalence of vitamin D deficiency(40% vs 20%, respectively) and insufficiency(70% vs 50%, respectively). Histologic inflammation was significantly higher in visually diseased mucosa from IBD patients(1.95 ± 0.25) than in normalappearing mucosa from control patients(0.25 ± 0.08, P < 0.01) and from IBD patients(0.65 ± 0.36, P < 0.05) and correlated inversely with VDR expression in visually diseased colonic tissue from IBD patients(r =-0.44, P < 0.05) and from IBD patients with Crohn's disease(r =-0.69, P < 0.05), but not in normal-appearing colonic tissue from control patients or IBD patients. Control and IBD patient serum vitamin D levels correlated positively with VDR expression in normal colon from control and IBD patients(r = 0.38, P < 0.05) and with patient age(r = 0.54, P < 0.01). CONCLUSION: Levels of serum vitamin D correlate positively with colonic VDR expression in visually normal mucosa whereas inflammation correlates negatively with colonic VDR expression in visually diseased mucosa in Puerto Rican patients.
文摘Objective To investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population. Method One hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI. Results The frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms. Conclusion The BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.
文摘Objective:Vitamin D receptor(VDR)mediates vitamin D activity.We examined whether VDR expression in excised melanoma tissues is associated with VDR gene(VDR)polymorphisms.Methods:We evaluated VDR protein expression(by monoclonal antibody immunostaining),melanoma characteristics,and carriage of VDR-Fok I-rs2228570(C>T),VDR-Bsm I-rs1544410(G>A),VDR-ApaI-rs7975232(T>G),and VDR-TaqI-rs731236(T>C)polymorphisms(by restriction fragment length polymorphism).Absence or presence of restriction site was denoted by a capital or lower letter,respectively:"F"and"f"for Fok I,"B"and"b"for Bsm I,"A"and"a"for ApaI,and "T"and"t"for TaqI endonuclease.Seventy-four Italian cutaneous primary melanomas(52.1±12.7 years old)were studied;51.4% were stage Ⅰ,21.6% stage Ⅱ ,13.5% stage Ⅲ,and 13.5% stage Ⅳ melanomas.VDR expression was categorized as follows:100% positive vs.<100%;over the median 20%(high VDR expression)vs.≤20%(low VDR expression);absence vs.presence of VDR-expressing cells.Results:Stage I melanomas,Breslow thickness of<1.00 mm,level II Clark invasion,Aa heterozygous genotype,and AaTT combined genotype were more frequent in melanomas with high vs.low VDR expression.Combined genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.<100%VDR-expressing cells.Combined genotype AATT was more frequent in melanomas lacking VDR expression(odds ratio=14.5;P=0.025).VDR expression was not associated with metastasis,ulceration,mitosis>1,regression,tumor-infiltrating lymphocytes,tumoral infiltration of vascular tissues,additional skin and non-skin cancers,and melanoma familiarity.Conclusions:We highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells.Low VDR expression in AATT carriers is a new finding that merits further study.VDR expression possibly poses implications for vitamin D supplementation against melanoma.VDR expression and VDR genotype may become precise medicinal tools for melanoma in the future.
文摘Aim: To investigate the single nucleotide polymorphism of vitamin D receptor (VDR) gene start codon in the Han nationality in Hubei and its relationship to the susceptibility to prostate cancel (PCa). Methods: The VDR genotypes were determined by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 80 patients with PCa and 96 normal male controls from the Han nationality in Hubei, using endonuclease Fok. Direct sequencing was done in part of the PCR products. Results: The frequency distribution of Fok I alleles in this cohort all followed the Hardy-Weinberg equilibrium. The distribution of genotypes and alleles had no significant difference between PCa patients and the controls (P>0.05). Conclusion: There was no significant relationship between Fok I polymorphism of VDR gene start codon and PCa in the Han nationality in Hubei.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for these reasons,it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment.The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled;consequently,at moment there are not effective treatments.In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis,to the vitamin D/vitamin D receptor(VD/VDR)axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD.However,the data currently available,including clinical trials with VD supplementation,still provides a contrasting picture.The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR.Based on recent data from literature,we focused in particular on the hypothesis that VDR itself,independently from its traditional ligand VD,may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
基金Supported by the National Natural Science Foundation of China (30700685)the Medical Science and Technology Research Project of Chongqing Municipal Health Bureau (2009-1-06)
文摘Background:The vitamin D receptor(VDR) gene is a primary candidate gene for tuberculosis susceptibility,but results of previous studies are somewhat contradictory and underpowered.Thus,it is essential to further explore the association between VDR gene polymorphisms and risk of pulmonary tuberculosis(PTB).Methods:A systematic review and meta-analysis about the association between FokI,TaqI,ApaI and BsmI polymorphisms and PTB susceptibility was conducted.Statistical Package for Social Science(Version 13.0) and Review Manager(Version 4.2,The Cochrane Collaboration) were used to analyze the data reported in studies.Results:A total of 13 studies with 2 262 cases and 2 833 controls were involved in the FokI polymorphism,and the results showed FokI polymorphism was associated with PTB susceptibility(allele f vs F:OR=1.12,95% CI=[1.02,1.23];the additive effect model ff vs FF:OR=1.40,95%CI=[1.10,1.77];the recessive genetic model ff vs Ff+FF:OR=1.39,95%CI=[1.12,1.71]).No significant associations were observed between TaqI(15 studies with 3 031 cases and 3 132 controls),ApaI(7 studies with 1 495 cases and 1 922 controls),BsmI(6 studies with 919 cases and 1 250 controls) variants and PTB susceptibility.Conclusion:We found variant FokI polymorphism of VDR gene may play a risky role in PTB development,and the genetic model was presumed to be recessive.
基金supported in part by Key Grant of the National Natural Science Foundation of China (No. 30730080)National Natural Science Foundation of China (No. 30972541, 30901233)+1 种基金National Outstanding Youth Science Foundation of China (No. 30425001)Key Laboratory of Laboratory Mecicine of Jiangsu Province (No. XK200731)
文摘客观维生素 D 和它的受体(VDR ) 在多重细胞的过程包含并且在恶意的开始和前进起一个重要作用。因此，我们假设了在 VDR 的层次和单个核苷酸多型性(SNP ) 可能具有在非小的房间肺癌症(NSCLC ) 的预示的意义的那血浆维生素 D。我们检验了血浆 25-hydroxyvitamin D 的方法[25 (哦) D ] 在 87 个病人的层次用连接酶的 immunosorbent 试金(ELISA ) 和 genotyped 与 NSCLC 诊断了在在伊卢米纳·戈尔登上的 568 个 NSCLC 病人的 VDR 的七潜在地功能的 SNP 门站台。有更高的血浆的结果病人 25 (哦) D 层次与更低的比病人有更坏的幸存(为趋势 = 的 P 0.048 ) 。rs1544410 和 rs739837 的 SNP 独立地与 NSCLC 幸存被联系(调整 HR = 1.61，为 rs739837 AA 对 AC/CC 和调整 HR = 的 95% CI = 1.06-2.45 1.51，为 rs1544410 AG/AA 对 GG 的 95% CI = 1.06-2.16 ) 。联合效果在 rs1544410 和 rs739837 和当带的不利遗传型病人的数字增加了，提高的死亡的风险之间被观察(为趋势 = 的 P 0.003 ) 。在 VDR 多型性和血浆之间没有重要协会 25 (哦) D 层次。结论我们的调查结果显示那血浆 25 (哦) D 层次和 VDR 的基因变体可以在这张中国人口为 NSCLC 用作预示的标记。
基金Supported by the Public Health Service grants, No. R01CA-51932 to RMB (National Cancer Institute)Center for Colon Cancer Research grant, No. RR017698 to FGB from National Institutes of Health, Department of Health and Human Services
基金Supported by National Natural Science Foundation of China(No.81170825)
文摘AIM: To observe the expression of vitamin D receptor(VDR) in human specimen and immortalized human corneal epithelium cells(HCEC) when challenged with fusarium solani. Moreover, we decided to discover the pathway of VDR expression. Also, we would like to detect the expression of cathelicidin antimicrobial peptide(CAMP) in the downstream pathway of VDR.·METHODS: Immunohistochemistry was used to examine the VDR expression in HCEC from healthy and fungal keratitis patients. Real time quantitative polymerase chain reaction(qPCR) was performed to observe the messenger ribonucleic acid(mRNA) change of VDR when immortalized HCEC were challenged with fusarium solani for different hours. CAMP was detected at both m RNA and protein levels.·RESULTS: We found out that the VDR expression in fusarium solani keratitis patients' specimen was much more than that in healthy people. The m RNA and protein expression of VDR increased when we stimulated HCEC with fusarium solani antigen(P <0.01) and it could be inhibited by toll like receptor 2(TLR2) monoclonal antibody. The CAMP expression was decreased because of fusarium solani antigen stimulation(P <0.01).·CONCLUSION: The VDR expression can be increased via TLR2/1-VDR pathway while the CAMP expression is decreased by the stimulation of fusarium solani antigen.
基金This project was supported by the National Natural ScienceFoundation of China ( Serial No:3 0 2 0 0 2 83 )
文摘To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene’s promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.
文摘Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.
文摘Colorectal cancer represents the third cancer worldwide. Studies showed thatinsufficient levels of vitamin D may result in colorectal cancer. Genetic variations in genes controlling vitamin D activity would play a role in determining susceptibility to colorectal cancer. Aim of the work: to study the different genotypes of VDR polymorphisms and detect the association between serum levels of 25(OH)VitD and 1,25(OH)2VitD among sample of Egyptian patients with different stages of colorectal cancer. Methods: Ninety patients (60 with different stages of colorectal cancer and 30 patients with benign pathology of the colon) together with 30 healthy controls were examined using PCR-RFLP analysis for FokI, ApaI and TaqI polymorphisms. Results: Genotype distribution for ApaI polymorphism showed no statistically significant difference between patients (colorectal cancer and benign) and controls with p = 0.1. There was no statistically significant difference in FokI polymorphism where p = 0.26 and genotype distribution for TaqI was also insignificant with p = 0.016. The median serum level of 25(OH)VitD was low in cancer cases compared to the control group and benign cases with (p 0.001). There was no statisticallysignificant difference of median serum level of 1,25(OH)2VitD between benign and cancer cases. There was statistically significant difference of median serum level of 25(OH)VitD and 1,25(OH)2VitD between stage I and stage II with (p = 0.004) and (p 0.001), and between stage I and stage III with (p = 0.001)and (p 0.001), but no statistically significant difference between stage II and III with (p = 0.514). Conclusions: There is ethnic variability in vitamin D receptor gene polymorphisms. The lack of significant association of the studied gene polymorphism in our population suggests that its association with other functionally known gene polymorphism might have a role in the pathogenesis of colorectal cancer.
