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
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
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
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
Metabolic Syndrome (MS) is a combination of multiple complex diseases, whose etiology is complicated and has many influencing factors Randomized controlled trials have shown that vitamin D supplementation could delay ...Metabolic Syndrome (MS) is a combination of multiple complex diseases, whose etiology is complicated and has many influencing factors Randomized controlled trials have shown that vitamin D supplementation could delay the ameliorate symptoms of multiple chronic disease Therefore, it is reasonable to postulate that the expression levels of vitamin D and its related gene variants might be correlated with MS.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
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
Objective:To investigate the relationship between vitamin D receptor gene polymorphism and prognosis in patients with end stage renal disease(ESRD)undergoing dialysis.Methods:80 patients with ESRD who underwent regula...Objective:To investigate the relationship between vitamin D receptor gene polymorphism and prognosis in patients with end stage renal disease(ESRD)undergoing dialysis.Methods:80 patients with ESRD who underwent regular hemodialysis in our hospital were admitted from January 2016 to June 2016,and 80 healthy volunteers from our hospital were collected as control group during the same period.The polymorphisms of rs1544410(BsmI)of vitamin D receptor gene were identified by peripheral blood DNA amplification and specific enzyme digestion,including wild type GG(bb)and mutant GA(Bb)and AA(BB).Then analyze and compare the distribution of BsmI in patients with ESRD and normal volunteers,further analyze the correlation between BsmI locus and clinical characteristics of patients with ESRD,and analyze the relationship between BsmI locus and prognosis of patients with ESRD according to the follow-up results of patients.Results:The incidence of wild type(bb)of vitamin D receptor BsmI locus in patients with ESRD was significantly lower than that in the control group,while the incidence of mutant type(Bb and BB)was higher than that in the control group,with an advantage ratio of 1.378(P=0.004).The allele frequency of BsmI locus showed that the incidence of A-base in patients with ESRD was higher than that in control group,with an advantage ratio of 1.368(P=0.010).Comparing the genotype and clinical characteristics of BsmI locus in patients with ESRD,it was found that there were no differences in age,sex ratio between men and women,BMI,hypertension,diabetes,LDL,HDL,TG,urea nitrogen,creatinine,calcium,phosphorus,albumin and vitamin D levels among different genotypes.One year after treatment,the survival rate of bb group was significantly higher than that of Bb group and BB group(P=0.006).K-M analysis showed that the median survival time of BB group was 20 months,that of BB group was 8 months,and that of BB group was 4 months(P=0.000).Conclusion:There is a high mutation rate of BsmI locus(GA,AA type)in patients with ESRD,that is,the mutation rate of G-base to A is higher,and the survival time of patients with mutation is significantly shortened.展开更多
Vitamin D&vitamin D receptor(VDR)signaling play a very crucial role in early embryonic heart development.We construct this case-control study to investigate the association between maternal serum vitamin D level&a...Vitamin D&vitamin D receptor(VDR)signaling play a very crucial role in early embryonic heart development.We construct this case-control study to investigate the association between maternal serum vitamin D level&VDR gene Fok1 polymorphism and risk of congenital heart defects(CHD)in offspring.Fifty mothers who had term neonates with CHD were considered as cases.Fifty age-comparable healthy mothers who had neonates without CHD were contemplated as controls.Maternal serum 25 hydroxyvitamin D[25(OH)D]level was tested using ELISA.Maternal VDR gene Fok1 polymorphism was analyzed using PCR-based RFLP-assay.There was a significant decrease in maternal vitamin D level(P=0.002)and a significant increase in vitamin D deficient status(P=0.007)among cases when compared to controls.VDR gene Fok1 genotypes distribution frequency were in accordance with Hardy Weinberg equilibrium(HW)among controls.A significant increase in VDR gene Fok1 F/f&f/f genotypes and f allele were observed in cases compared to controls with estimated odds ratio(95%confidence interval)&P-value of 3(1e8)&P=0.006,11(1e97)&P=0.01 and 3(2e6)&P=0.001 respectively.There was a significant decrease in maternal vitamin D level in neonates with cyanotic CHD(P=0.000)compared to those with a cyanotic CHD while there was no significant difference in VDR Fok1 genotype(P=0.18)&allele(P=0.05)distribution between two groups.We concluded that maternal vitamin D deficiency and VDR gene Fok1 F/f,f/f genotype and f allele were associated with increased risk of CHD in offspring.展开更多
BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis...BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.展开更多
In recent years,more and more reports have been reported on the extracellular role of vitamin D signaling pathway.Studies have shown that both genomic and non-genomic effects of vitamin D signaling pathway are involve...In recent years,more and more reports have been reported on the extracellular role of vitamin D signaling pathway.Studies have shown that both genomic and non-genomic effects of vitamin D signaling pathway are involved in calcium homeostasis,skeletal effects,cell proliferation,differentiation,oxidative stress,angiogenesis,inflammatory response,immune regulation,production and recognition of antimicrobial peptides to varying degrees.This paper reviews the research progress of key genes such as GC,CYP2R1,CYP24A1,CYP27B1,VDR and RXRαin vitamin D receptor signaling pathway,in order to understand the physiological and pathological mechanisms of this pathway more accurately and comprehensively,and lay a foundation for further research.展开更多
Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,...Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.展开更多
Polymorphyism in vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass Its role within various ethnic populations is not clear The purpose of this study...Polymorphyism in vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass Its role within various ethnic populations is not clear The purpose of this study was to determine the frequencies of VDR genotypes in the Han and Uygur nationalities in China Methods We analyzed the polymorphism of BsmⅠ restriction enzyme by PCR-RFLP technique in 162 healthy postmenopausal women of the Han nationality and 50 healthy postmenopausal women of the Uygur nationality in China The genotype frequencies of VDR were calculated using Hardy-Weinberg equilibrium formula Results In the Han nationality, the bb, Bb, and BB genotype accounted for 91 36%, 8 64% and 0%, respectively In the Uygur nationality, frequencies were 74 00%, 18 00% and 8 00%, respectively Conclusion There was a significant difference between the Han and Uygur nationalities in the frequency distribution of VDR genotype ( P <0 01) Compared with the Caucasian population in the United States, Australia and France, there was a similar value to Uygur nationality in the BB genotype This investigation gave us further evidence on the different etiopathology of osteoporosis in various ethnic展开更多
In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and ...In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor(VDR)gene polymorphisms from PubMed,Web of Science,Cochrane Library,and Embase databases.We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity.Furthermore,higher vitamin D concentrations are linked to better cognitive function and mood in PD patients.Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent,but the Fokl(C/M)polymorphism is significantly linked with PD.The occurrence of Fokl(CT)gene polymorphism may influence the risk,severity,and cognitive ability of PD patients,while also possibly influencing the effect of Vitamin D3 supplementation in PD patients.In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission,interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.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
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
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
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.
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.
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 the National Nature Science Foundation of China [grants number 81872626,81573151,U1204823,and 81573243]Science and Technology Foundation for Innovation Talent of Henan Province [grants number 1542005 10010]Dietary Nutrition Research and Education Foundation of Danone [grants number DIC2013-06]
文摘Metabolic Syndrome (MS) is a combination of multiple complex diseases, whose etiology is complicated and has many influencing factors Randomized controlled trials have shown that vitamin D supplementation could delay the ameliorate symptoms of multiple chronic disease Therefore, it is reasonable to postulate that the expression levels of vitamin D and its related gene variants might be correlated with MS.
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 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.
基金Innovation of medical research youth of Sichuan Medical Association Project(No.Q15007).
文摘Objective:To investigate the relationship between vitamin D receptor gene polymorphism and prognosis in patients with end stage renal disease(ESRD)undergoing dialysis.Methods:80 patients with ESRD who underwent regular hemodialysis in our hospital were admitted from January 2016 to June 2016,and 80 healthy volunteers from our hospital were collected as control group during the same period.The polymorphisms of rs1544410(BsmI)of vitamin D receptor gene were identified by peripheral blood DNA amplification and specific enzyme digestion,including wild type GG(bb)and mutant GA(Bb)and AA(BB).Then analyze and compare the distribution of BsmI in patients with ESRD and normal volunteers,further analyze the correlation between BsmI locus and clinical characteristics of patients with ESRD,and analyze the relationship between BsmI locus and prognosis of patients with ESRD according to the follow-up results of patients.Results:The incidence of wild type(bb)of vitamin D receptor BsmI locus in patients with ESRD was significantly lower than that in the control group,while the incidence of mutant type(Bb and BB)was higher than that in the control group,with an advantage ratio of 1.378(P=0.004).The allele frequency of BsmI locus showed that the incidence of A-base in patients with ESRD was higher than that in control group,with an advantage ratio of 1.368(P=0.010).Comparing the genotype and clinical characteristics of BsmI locus in patients with ESRD,it was found that there were no differences in age,sex ratio between men and women,BMI,hypertension,diabetes,LDL,HDL,TG,urea nitrogen,creatinine,calcium,phosphorus,albumin and vitamin D levels among different genotypes.One year after treatment,the survival rate of bb group was significantly higher than that of Bb group and BB group(P=0.006).K-M analysis showed that the median survival time of BB group was 20 months,that of BB group was 8 months,and that of BB group was 4 months(P=0.000).Conclusion:There is a high mutation rate of BsmI locus(GA,AA type)in patients with ESRD,that is,the mutation rate of G-base to A is higher,and the survival time of patients with mutation is significantly shortened.
文摘Vitamin D&vitamin D receptor(VDR)signaling play a very crucial role in early embryonic heart development.We construct this case-control study to investigate the association between maternal serum vitamin D level&VDR gene Fok1 polymorphism and risk of congenital heart defects(CHD)in offspring.Fifty mothers who had term neonates with CHD were considered as cases.Fifty age-comparable healthy mothers who had neonates without CHD were contemplated as controls.Maternal serum 25 hydroxyvitamin D[25(OH)D]level was tested using ELISA.Maternal VDR gene Fok1 polymorphism was analyzed using PCR-based RFLP-assay.There was a significant decrease in maternal vitamin D level(P=0.002)and a significant increase in vitamin D deficient status(P=0.007)among cases when compared to controls.VDR gene Fok1 genotypes distribution frequency were in accordance with Hardy Weinberg equilibrium(HW)among controls.A significant increase in VDR gene Fok1 F/f&f/f genotypes and f allele were observed in cases compared to controls with estimated odds ratio(95%confidence interval)&P-value of 3(1e8)&P=0.006,11(1e97)&P=0.01 and 3(2e6)&P=0.001 respectively.There was a significant decrease in maternal vitamin D level in neonates with cyanotic CHD(P=0.000)compared to those with a cyanotic CHD while there was no significant difference in VDR Fok1 genotype(P=0.18)&allele(P=0.05)distribution between two groups.We concluded that maternal vitamin D deficiency and VDR gene Fok1 F/f,f/f genotype and f allele were associated with increased risk of CHD in offspring.
基金Supported by the Key Research and Development Projects in Sichuan Province,No.2021YFS0168the National Scientific and Technological Major Project for Infectious Diseases Control in China,No.2018ZX10715-003.
文摘BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.
基金National Natural Science Foundation of China(No.81860551)Key Research and Development Project of Hainan Province(No.ZDYF2018156)。
文摘In recent years,more and more reports have been reported on the extracellular role of vitamin D signaling pathway.Studies have shown that both genomic and non-genomic effects of vitamin D signaling pathway are involved in calcium homeostasis,skeletal effects,cell proliferation,differentiation,oxidative stress,angiogenesis,inflammatory response,immune regulation,production and recognition of antimicrobial peptides to varying degrees.This paper reviews the research progress of key genes such as GC,CYP2R1,CYP24A1,CYP27B1,VDR and RXRαin vitamin D receptor signaling pathway,in order to understand the physiological and pathological mechanisms of this pathway more accurately and comprehensively,and lay a foundation for further research.
基金This work was supported by grant from National Research Centre,Egypt(16361).
文摘Vitamin D deficiency might contribute to the pathogenesis of metabolic syndrome and could cause immune disturbance.The aim of this study is to analyze the associations between Vitamin D receptor(VDR)gene polymorphism,serum 25-hydroxy vitamin D,metabolic and inflammatory biomarkers in Egyptian obese women.The study included 201 obese women with vitamin D deficiency and 249 obese matched age healthy controls with sufficient vitamin D levels.Their age ranged between 25 and 35 years.Inflammatory biomarkers(interleukin-6 and C-reactive protein)and serum 25(OH)D were measured by enzyme-linked immunosorbent assay.Insulin resistance(IR)was determined by the homeostasis model assessment of insulin resistance(HOMA-IR).Vitamin D receptor(VDR)gene polymorphisms of FokI,ApaI,and TaqI were studied by PCR using the restriction fragment length polymorphism(RFLP)technique.Obese women with vitamin D deficiency had significant higher values of inflammatory and metabolic parameters compared to controls.Multivariable-logistic regression showed associations between 25(OH)D deficiency and metabolic components when comparing cases with controls.Moreover,cases carrying polymorphic alleles showed significant lower levels of serum 25(OH)D and higher HOMA-IR,blood pressure levels and lipid parameters compared to those with the wild type homozygote in obese cases with vitamin D deficiency.Vitamin D deficiency in Egyptian obese women with vitamin D deficiency is associated with abnormal metabolic components and abnormal inflammatory biomarkers.Moreover,VDR polymorphisms play important role in immune and inflammation status.
基金ThisprojectwassupportedbytheFoundationoftheScienceandTechnologyofNationalDefence (No 97J0 0 0 3 JB10 0 1)
文摘Polymorphyism in vitamin D receptor (VDR) gene has been reported to play a major role in variations for genetic regulation of bone mass Its role within various ethnic populations is not clear The purpose of this study was to determine the frequencies of VDR genotypes in the Han and Uygur nationalities in China Methods We analyzed the polymorphism of BsmⅠ restriction enzyme by PCR-RFLP technique in 162 healthy postmenopausal women of the Han nationality and 50 healthy postmenopausal women of the Uygur nationality in China The genotype frequencies of VDR were calculated using Hardy-Weinberg equilibrium formula Results In the Han nationality, the bb, Bb, and BB genotype accounted for 91 36%, 8 64% and 0%, respectively In the Uygur nationality, frequencies were 74 00%, 18 00% and 8 00%, respectively Conclusion There was a significant difference between the Han and Uygur nationalities in the frequency distribution of VDR genotype ( P <0 01) Compared with the Caucasian population in the United States, Australia and France, there was a similar value to Uygur nationality in the BB genotype This investigation gave us further evidence on the different etiopathology of osteoporosis in various ethnic
基金The authors of this review were supported by the National Natural Science Foundation of China(81971201)the National Science Foundation of Hunan Province(2019J40450).
文摘In recent years,many studies have investigated the correlations between Parkinson's disease(PD)and vitamin D status,but the conclusion remains elusive.The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor(VDR)gene polymorphisms from PubMed,Web of Science,Cochrane Library,and Embase databases.We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity.Furthermore,higher vitamin D concentrations are linked to better cognitive function and mood in PD patients.Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent,but the Fokl(C/M)polymorphism is significantly linked with PD.The occurrence of Fokl(CT)gene polymorphism may influence the risk,severity,and cognitive ability of PD patients,while also possibly influencing the effect of Vitamin D3 supplementation in PD patients.In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission,interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.
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.
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.
