VDR基因单核苷酸多态性与大骨节病关联分析

目的探讨VDR基因2个SNP位点多态性与大骨节病的关联关系。方法选取64例大骨节病患者和60例健康人群为病例组和对照组,对所选基因的两个SNP位点进行基因分型,计算相应人群中2个位点的基因型频率、单位点等位基因频率,比较各组间基因型频率、单位点等位基因频率的差异。结果 rs2254210和rs2189480在基因型频率、单位点等位基因频率及单倍型重构分析中与大骨节病均无显著性关联。结论 在后续的研究中进一步增大样本量和SNP标记密度,进行全基因关联分析,以验证VDR基因与大骨节病的相关性。

Vitamin D receptor gene polymorphisms and colorectal cancer risk:A systematic meta-analysis

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.

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

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.

Association between gene polymorphisms of vitamin D receptor and pulmonary tuberculosis susceptibility:a meta-analysis

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 Fok[, TaqI, Apal and Bsm[ 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 firs 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 Fokl polymorphism of VDR gene may play a risky role in PTB development, and the genetic model was presumed to be recessive.

Vitamin D receptor gene Tru9I polymorphism and risk for incidental sporadic colorectal adenomas

AIM： Recent laboratory and epidemiological studies suggest that vitamin D is a potential agent for colorectal cancer prevention. Its function is partially mediated by the vitamin D receptor （VDR）. The aim of this study was to investigate whether a novel G （allele ‘U’g〉A （allele ‘u’ polymorphism （Tru9I） in the VDR intron 8 region is associated with risk for colorectal adenoma in a colonoscopy-based case-control study. METHODS： Genotyping for a total of 391 subjects was carried out through PCR and restriction fragment length polymorphism. RESULTS： The frequencies of ‘U’ and ‘u’ alleles were 89.3% and 10.7%, respectively. The ‘Uu’ and ‘uu’ genotypes were associated with decreased risk for adenoma （OR, 0.71; 95%CI, 0.40-1.25）. The inverse association was more pronounced for multiple adenomas and adenomas that were larger had moderate or greater dysplasia, or were sessile： the odds ratios （ORs） were, 0.51 （95%CI, 0.21-1.24）, 0.37 （95%CI, 0.11-1.28）, 0.68 （95%CI, 0.33- 1.41）, and 0.36 （95%CI, 0.13-0.97） respectively. In joint/ combined analyses, inverse associations were more obvious among those who had at least one ‘u’ allele and also were younger （OR, 0.60; 95%CI, 0.26-1.37）, women （OR, 0.38; 95%CI, 0.17-0.88）, did not smoke （OR, 0.39; 95%CI, 0.13-1.23）, or took NSAID （OR, 0.38; 95%CI, 0.12-1.25）, but no evidence existed for interactions with calcium or vitamin D intake.CONCLUSION： Our findings suggest that the VDR TrugI polymorphism may be associated with lower risk for colorectal adenoma, particularly in interaction with various risk factors, but not with calcium or vitamin D.

Theoretical basis of a beneficial role for vitamin D in viral hepatitis

Abnormal bone metabolism and dysfunction of the calcium-parathyroid hormone-vitamin D axis have been reported in patients with viral hepatitis. Some studies suggested a relationship between vitamin D and viral hepatitis. Genetic studies have provided an opportunity to identify the proteins that link vitamin D to the pathology of viral hepatitis (i.e., the major histocompatibility complex class Ⅱ molecules, the vitamin D receptor, cytochrome P 450 , the renin-angiotensin system, apolipoprotein E, liver X receptor, toll-like receptor, and the proteins regulated by the Sp1 promoter gene). Vitamin D also exerts its effects on viral hepatitis via non-genomic factors, i.e., matrix metalloproteinase, endothelial vascular growth factor, prostaglandins, cyclooxygenase-2, and oxidative stress. In conclusion, vitamin D could have a beneficial role in viral hepatitis. Calcitriol is best used for viral hepatitis because it is the active form of the vitamin D 3 metabolite.

Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients

Objective To clarify the role of vitamin D receptor (VDR) expression in parathyroid proliferation and resistance of parathyroid glands to 1,25(OH) 2D 3 with secondary hyperparathyroidism (SHPT) Methods This study used archive parathyroid with 7 uremic patients The expression of proliferation cell nuclear antigen (PCNA) and VDR was evaluated in nineteen surgically excised parathyroid tissues, including 11 diffuse hyperplasia (DH type) and 8 nodular hyperplasia (NH type) of parathyroid glands, by immunohistochemistry (avidin biotin complex method) Results The weight of parathyroid in SHPT was remarkably increased by 16 1 times The numbers of parathyroid cells were increased by 1 86 times The rate of PCNA was remarkably increased in parathyroid hyperplasia with SHPT compared with that in control group [(6 35±3 36)‰ vs (1 73±1 31)‰, P <0 001] The number of PCNA in DH type was lower than that in NH type ( P <0 001) The density of VDR in the parathyroid with SHPT was significantly decreased [(40 28±13 13)% vs (83 79±3 77)%, P <0 001], VDR immunoreactivity expression in NH type was lower than that in DH type [(27 14±4 12)% vs (49 84±7 33)%, P <0 001] A significantly negative correlation was found between VDR density and the weight of the parathyroid ( r =-0 46, P <0 05), the same as VDR and PCNA ( r = -0 75, P <0 001) Conclusion VDR density was significantly decreased in parathyroid tissue of uremic patients showing nodular hyperplasia compared with that in diffuse hyperplasia and there was significantly negative correlation between VDR density and the weight of the parathyroid, and this may contribute to the progression of SHPT Furthermore, VDR deficiency may cause the resistance of parathyroid cells to 1, 25(OH) 2D 3, in part

Vitamin Dreceptor gene polymorphism and bone mineral density in patients with type 2 diabetes mellitus

Objective To explore the relationship between vitamin D receptor(VDR)gene polymorphisms and bone mineral density(BMD)in patients with type 2 diabetes mellitus(DM)and to better understand the pathogenesis of osteoporosis.Methods Ninety seven patients with type 2 DM were recruited for this study.BMD was measured by single photon absorptiometry at the lower one third of the nondominant radius and ulna.Polymorphisms of the VDR gene were analyzed by DNA amplification with polymerase chain reaction(PCR)and endonuclease digestion with Bsm Ⅰ.Results The respective frequencies of VDR genotypes were BB 18.6%,Bb 27.8% and bb 53.6%.The Z scores of the three groups were - 1.57 ± - 0.60,- 1.45 ± - 0.67 and - 1.41 ± - 0.81,respectively.Although the BMD of the Bb genotype DM patients was higher than that of BB genotype DM patients and lower than that of bb genotype DM patients,there were no significant differences.Conclusion These findings suggest a small influence of VDR gene polymorphism on the BMD of patients with type 2 DM.Further study on the value of VDR genotypes in the pathogenesis of osteoporosis in diabetes mellitus is still needed.

Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases

Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.