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Polymorphisms of the vitamin d receptor Gene and Sexdifferential Associations with Lipid Profiles in Chinese Han Adults

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Biomedical and Environmental Sciences 2022年第2期35卷 115-125页

作者： CHEN Yan Mei XU Ping WANG Zhou Tian ZHU Yu Mei GONG Chun Mei HUANG Chang Hua LIU Xiao Li ZHOU Ji Chang School of Public Health(Shenzhen) Sun Yat-sen UniversityShenzhen 518100GuangdongChina Shenzhen Center for Chronic disease Control Shenzhen 518020GuangdongChina Shenzhen Qilinshan Sanatorium Shenzhen 518055GuangdongChina Guangdong Province Engineering Laboratory for Nutrition Translation Guangzhou 510080GuangdongChina

Objective To explore the association of single nucleotide polymorphisms(SNPs)of the vitamin d receptor gene(VdR)with circulating lipids considering gender *** 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 *** 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 *** 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(Pdyslipidemia and 564 without dyslipidemia),the recessive model of Cdx2 and the additive and recessive models of Fok1 differed(PdLC-classified subgroups,respectively,and Fok1 BB and Cdx2 TT presented interactions with 25OHd in the negative associations with HdLC(Pdults 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 *** interaction of Vd and Fok1 BB or Cdx2 TT in males synergistically decreased HdLC levels.

关键词： vitamin d vitamin d receptor Gene polymorphism Lipid dyslipidemia

Bsm I(rs1544410) and Fok I(rs2228570) vitamin d receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

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Cancer Biology & Medicine 2017年第3期14卷 302-318页

作者： Sabina Cauci Vincenzo Maione Cinzia Buligan Martina Linussio diego Serraino Giuseppe Stinco department of Medicine University of UdineUdine 33100Italy dermatology Clinic University Hospital of Brescia Brescia 25123Italy dermatology Clinic University Hospital of UdineUdine 33100Italy Unit of Cancer Epidemiology CRO Aviano National Cancer InstituteAviano 33081Italy

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 ***: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 *** polymorphisms were measured by restriction fragment length polymorphism *** or presence of Bsm I and Fok I restriction sites was denoted by"B"and"F"or by"b"and"f,"***:VdR-Bsm I bb genotype was more frequent among Met M(32.7%)than among NMet M cases(13.2%),with odds ratio(OR)=*** 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 *** suggest gene-environment implications in melanoma susceptibility and *** studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.

关键词： vitamin d receptor VdR polymorphism cutaneous melanoma metastatic melanoma smoking body mass index obesity skin cancer

Immunohistochemical evaluation of vitamin d receptor(VdR) expression in cutaneous melanoma tissues and four VdR gene polymorphisms

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Cancer Biology & Medicine 2017年第2期14卷 162-175页

作者： Francesco La Marra Giuseppe Stinco Cinzia Buligan Giovanni Chiriacò diego Serraino Carla di Loreto Sabina Cauci department of Medical Area School of MedicineUniversity of Udine dermatology Clinic Udine University-HospitalUniversity of Udine Unit of Cancer Epidemiology CRO Aviano National Cancer Institute

Objective:vitamin d receptor(VdR)mediates vitamin d *** examined whether VdR expression in excised melanoma tissues is associated with VdR gene(VdR)***: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 ***-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 *** expression was categorized as follows:100% positive vs.dian 20%(high VdR expression)vs.≤20%(low VdR expression);absence *** of VdR-expressing ***:Stage I melanomas,Breslow thickness ofd AaTT combined genotype were more frequent in melanomas with high *** VdR *** genotypes BbAA,bbAa,AATt,BbAATt,and bbAaTT were more frequent in 100%vs.dR-expressing *** 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 ***:We highlighted that VdR polymorphisms can affect VdR expression in excised melanoma *** VdR expression in AATT carriers is a new finding that merits further *** expression possibly poses implications for vitamin d supplementation against *** expression and VdR genotype may become precise medicinal tools for melanoma in the future.

关键词： vitamin d receptor VdR protein expression VdR polymorphism cutaneous melanoma metastatic melanoma skin cancer predictive biomarkers FokI polymorphism

MiR-125a-5p Regulates vitamin d receptor Expression in a Mouse Model of Experimental Autoimmune Encephalomyelitis

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Neuroscience Bulletin 2020年第2期36卷 110-120页

作者： Han-Chun Long Rui Wu Chun-Feng Liu Fei-Long Xiong Zu Xu dian He Yi-Fan Zhang Bing Shao Ping-An Zhang Guang-Yin Xu Lan Chu department of Neurology The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550001China department of Neurology The Second Affiliated Hospital of Soochow UniversitySuzhou 215008China Institute of Neuroscience Soochow UniversitySuzhou 215123China department of Neurology The Affiliated Xingyi City Hospital of Guizhou Medical UniversityXingyi 562400China

Multiple sclerosis(MS)is a chronic and incurable autoimmune neurodegenerative disease of the central nervous *** the symptoms of MS can be managed by vitamin d3 treatment alone,this condition cannot be completely ***,there might be unknown factors capable of regulating the vitamin d receptor(VdR).Genome-wide analysis showed that miRNAs were associated with *** sought to determine the role and mechanism of action of miRNA-125a-5p and VdRs in a model of MS,mice with experimental autoimmune encephalomyelitis(EAE),which was induced by myelin oligodendrocyte glycoprotein 35–55 *** mice showed decreased mean body weight but increased mean clinical scores compared with vehicle or control *** inflammatory infiltration was found in the lumbosacral spinal cord of EAE *** addition,VdR expression was significantly lower while the expression of miR-125a-5p was markedly higher in the spinal ventral horn of EAE mice than in vehicle or control ***,activation of VdRs by paricalcitol or inhibition of miR-125a-5p by its antagomir markedly decreased the mean clinical scores in EAE ***,VdR and miR-125a-5p were co-localized in the same neurons of the ventral *** importantly,inhibition of miR-125a-5p remarkably blocked the decrease of VdRs in EAE *** results support a critical role for miR-125a-5p in modulating VdR activity in EAE and suggest potential novel therapeutic interventions.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis vitamin d receptor MiR-125a-5p Myelin oligodendrocyte glycoprotein 35-55 peptides

Loss of the vitamin d receptor triggers senescence in chronic myeloid leukemia via ddIT4-mediated dNA damage

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Journal of Molecular Cell Biology 2023年第10期15卷 65-76页

作者： Yan Xu Wentao Qi Chengzu Zheng Yuan Li Zhiyuan Lu Jianmin Guan Chunhua Lu Baobing Zhao Key Lab of Chemical Biology(MOE) School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China NMPA Key Laboratory for Technology Research and Evaluation of drug Products School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China department of Pharmacology School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China School of Pharmaceutical Sciences&Institute of Materia Medica Shandong First Medical University&Shandong Academy of Medical SciencesJinan 250012China department of Hematology Heze Municipal HospitalHeze 274031China

Chronic myeloid leukemia(CML)is a hematopoietic malignancy driven by the fusion gene BCR::*** resistance to tyrosine kinase inhibitors(TKIs),due to BCR::ABL1 mutations and residual leukemia stem cells(LSCs),remains a major challenge in CML ***,we revealed the requirement of the vitamin d receptor(VdR)in the progression of *** was upregulated by BCR::ABL1 and highly expressed in CML ***,VdR knockdown inhibited the proliferation of CML cells driven by both BCR::ABL1 and TKI-resistant BCR::ABL1 ***,VdR transcriptionally regulated ddIT4 expression;reduced ddIT4 levels upon VdR knockdown triggered dNA damage and senescence via p53 signaling activation in CML ***,VdR deficiency not only suppressed tumor burden and progression in primary CML mice but also reduced the self-renewal capacity of ***,our study demonstrated that targeting VdR is a promising strategy to overcome TKI resistance and eradicate LSCs in CML.

关键词： vitamin d receptor senescence chronic myeloid leukemia ddIT4

Expression of vitamin d receptor and cathelicidin in human corneal epithelium cells during fusarium solani infection

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International Journal of Ophthalmology(English edition) 2015年第5期8卷 866-871页

作者： Lin Cong Yi-Ping Xia Gui-Qiu Zhao Jing Lin Qiang Xu Li-Ting Hu Jian-Qiu Qu Xu-dong Peng department of Ophthalmology the Affiliated Hospital of Qingdao University

AIMTo 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 *** 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 mRNA and protein *** found out that the VdR expression in fusarium solani keratitis patients' specimen was much more than that in healthy people. The mRNA and protein expression of VdR increased when we stimulated HCEC with fusarium solani antigen (Pd it could be inhibited by toll like receptor 2 (TLR2) monoclonal antibody. The CAMP expression was decreased because of fusarium solani antigen stimulation (PdR expression can be increased via TLR2/1-VdR pathway while the CAMP expression is decreased by the stimulation of fusarium solani antigen.

关键词： vitamin d receptor fusarium solani corneal epithelium cathelicidin

Is vitamin d receptor a druggable target for non-alcoholic steatohepatitis?

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World Journal of Gastroenterology 2020年第38期26卷 5812-5821页

作者： Ying Cao Xiang-Bing Shu Zemin Yao Guang Ji Li Zhang Institute of digestive diseases Longhua HospitalChina-Canada Center of Research for Digestive DiseasesShanghai University of Traditional Chinese MedicineShanghai 200032China department of Geratology Baoshan Branch of Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201999China department of Biochemistry Microbiology and ImmunologyUniversity of OttawaOttawa K1H8M5OntarioCanada

Nonalcoholic steatohepatitis(NASH)is a progressed stage of non-alcoholic fatty liver disease,and available therapeutic strategies for NASH are *** d receptor(VdR)is proposed as a druggable target for NASH due to the discovery of vitamin d deficiency in NASH *** 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 *** 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 *** 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 ***,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 *** 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.

关键词： vitamin d receptor Non-alcoholic steatohepatitis vitamin d Bile acids Inflammation Lipid metabolism

Association of vitamin d receptor Gene Polymorphisms with Calcium Oxalate Calculus disease

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第1期23卷 38-41页

作者：王少刚刘继红胡少群叶章群 departmentofUrology TongjiHospitalTongjiMedicalCollegeHuazhongUniversityofScienceandTechnology

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.

关键词： gene polymorphism vitamin d receptor calcium oxalate calculus hypercalciuria

Colonic vitamin d receptor expression is inversely associated with disease activity and jumonji domain-containing 3 in active ulcerative colitis

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World Journal of Gastroenterology 2020年第46期26卷 7352-7366页

作者： Hong-Qian Wang Wen-Hui Zhang Ya-Qi Wang Xiao-Pan Geng Ming-Wei Wang Yuan-Yuan Fan Jing Guan Ji-Long Shen Xi Chen department of Gastroenterology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022Anhui ProvinceChina department of Pathogen Biology Anhui Medical UniversityHefei 230032Anhui ProvinceChina

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 *** To study the relationship between VdR,Jmjd3 and H3K27me3 in patients with active *** One hundred patients with active UC and 56 healthy controls were enrolled in this *** 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 *** d levels were measured by *** mucosal tissues from UC patients and controls were collected by *** expression of VdR,Jmjd3 and H3K27me3 in the intestinal mucosa was determined by immunohistochemistry *** Patients with active UC had lower levels of serum vitamin d(13.7±2.8 ng/mL,Pvitamin 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(Pd negatively correlated with disease activity(r=-0.868,PdR expression were noted in the most serious lesion(defined as UC diseased)and 20 cm proximal to the anus(defined as UC normal)(Pd3 expression significantly increased in UC patients(Pdifference was found between the different sites in UC patients.H3K27me3 expression in UC patients was significantly down-regulated when compared with normal tissues(Pd in the mild disease activity group in comparison with the moderate disease activity group of UC patients(Pd3 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,Pvitamin d and VdR were inversely correlated with

关键词： vitamin d Ulcerative colitis disease activity vitamin d receptor Jumonji domain-containing 3 Trimethylated H3 lysine 27