Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study / Vitamina D, proteína de ligação à vitamina D, níveis de receptores de vitamina D e disautonomia cardíaca em pacientes com esclerose múltipla: um estudo transversal

ABSTRACT Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. Methods: The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. Results: The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = −0.406). Conclusion: There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

RESUMO A vitamina D é um hormônio esteroide pleiotrópico que modula o equilíbrio autonômico. Sua deficiência tem sido descrita como fator de risco ambiental para esclerose múltipla (EM). O objetivo deste estudo foi investigar os níveis séricos de vitamina D, proteína de ligação à vitamina D (VDBP) e receptor de vitamina D (VDR) e avaliar a disautonomia cardíaca em pacientes com EM devida à interação bidirecional entre vitamina D e sistema nervoso autônomo. Métodos: O presente estudo transversal foi realizado em 26 pacientes com EM remitente-recorrente e em 24 controles saudáveis. A variabilidade da pressão arterial ambulatorial (BPV) por 24 horas foi calculada e os participantes foram avaliados quanto à hipotensão ortostática e hipertensão supina. Os níveis séricos de vitamina D, VDBP e VDR foram medidos. Resultados: O nível sérico médio de vitamina D foi significativamente menor nos pacientes com EM do que nos controles (p = 0,044); no entanto, não houve diferença significativa em termos de níveis de VDR e VDBP entre os grupos. Hipertensão supina e hipotensão ortostática foram significativas e a BPV sistólica de 24 horas diminuiu significativamente em pacientes com EM (p < 0,05) em comparação aos controles. Não foi encontrada correlação entre vitamina D, VDBP e VDR com hipertensão supina, hipotensão ortostática e BPV sistólica (p > 0,05). Também houve correlação negativa entre VDBP e EDSS (p = 0,039, r = −0,406). Conclusão: Não houve correlação entre hipotensão ortostática, hipertensão supina e valores de BPV sistólica e vitamina D sérica, VDBP e VDR em pacientes com EM. Futuros estudos prospectivos com grande número de pacientes podem nos ajudar a entender melhor a relação entre vitamina D e sistema nervoso autônomo.

Vitamin D receptor in subcutaneous adipose tissue and serum vitamin D LeveLs reLate to gestationaL diabetes meLLitus in overweight/obese pregnant women / 中华围产医学杂志

Objective To investigate the differences in the expression of vitamin D receptor (VDR) and serum vitamin D levels in subcutaneous adipose tissue between overweight/obese and normal-weight gravidas, and the relationship between these two indicators and gestational diabetes mellitus (GDM). Methods Women with full-term singleton pregnancies who underwent elective cesarean section in Changzhou Maternal and Child Health Care Hospital Affiliated to Nanjing Medical University from January 2015 to April 2017 were enrolled. Among them, there were 70 cases GDM women, including 35 normal-weight (NW-GDM group) and 35 overweight/obese women (OW-GDM group). During the same period, another 70 pregnant women with normal glucose tolerance who underwent scheduled cesarean delivery were selected as the control group, including 35 normal weight women (NW-control group) and 35 obese/overweight women (OW-control group). Fasting blood samples were collected before operation to determine the levels of different biomarkers, including vitamin D, lipid, fasting blood glucose, fasting insulin and adiponectin, and to calculate the homeostasis model assessment-insulin resistance (HOMA-IR). Two subcutaneous adipose tissue samples of the abdominal wall were taken during the operation to detect the expression and distribution of VDR protein with immunohistochemistry. Meanwhile, VDR mRNA transcription level was quantitatively analyzed using real-time fluorescence quantitative polymerase chain reaction. One-way analysis of variance, LSD, Kruskal-Wallis test, Mann-Whitney U test, Chi-square test and logistic regression analysis were used for statistical analysis. ResuLts (1) The body mass index (BMI) of the OW-control group and the OW-GDM group before pregnancy and delivery were all higher than that of the NW-control group and the NW-GDM group [BMI before pregnancy: (29.2±2.9), (29.4±3.8) vs (21.1±2.3) and (21.9±2.0) kg/m2, F=87.766; BMI before delivery: (35.2±3.4), (35.1±4.3) vs (27.9±2.8) and (28.8± 3.3) kg/m2, F=44.827; all P<0.001]. Newborn birth weight and the proportion of diabetic family history in the OW-GDM group were higher comparing to the NW- and OW- control group [(3 893±498) vs (3 501±402) and (3 625±332) g, F=4.751; 22.9%(8/35) vs 5.7%(2/35) and 5.7%(2/35), χ2=7.869; all P<0.05]. (2) In the OW-control group, the fasting insulin level and HOMA-IR were higher and the adiponectin and vitamin D concentration were lower than those in the NW-control group [13.3(12.3-14.5) vs 12.0(10.4-13.3) mmol/L, 2.7(2.4-3.0) vs 2.2(2.0-2.7), (61.8±20.4) vs (74.9±29.3) ng/ml, (21.6±7.2) vs (25.9±7.3) ng/ml; all P<0.05], and similar results were found between the OW-GDM group and the NW-GDM group [15.3(12.3-19.5) vs 12.0(10.1-15.8) mmol/L, 3.4(2.6-4.1) vs 2.6(2.1-3.2), (50.3±22.3) vs (62.1±23.2) ng/ml, (17.1±6.7) vs (20.6±7.9) ng/ml, all P<0.05]. Compared with the NW-control group, the NW-GDM group had higher fasting glucose and lower high density lipoprotein-cholesterol (HDL-C), adiponectin and vitamin D levels [4.6(4.3-5.1) vs 4.3(4.0-4.5) mmol/L, 1.7(1.6-1.9) vs 2.1(1.6~2.4) mmol/L, (62.1±23.2) vs (74.9±29.3) ng/ml, (20.6±7.9) vs (25.9±7.3) ng/ml; all P<0.05]. Compared with the OW-control group, fasting glucose, fasting insulin and HOMA-IR were higher and HDL-C, adiponectin and vitamin D levels were lower in the OW-GDM group [4.7(4.4-5.4) vs 4.5(4.2-4.7) mmol/L, 15.3(12.3-19.5) vs 13.3(12.3-14.5) mmol/L, 3.4(2.6-4.1) vs 2.7(2.4-3.0), 1.6(1.4-1.8) vs 1.9(1.7-2.2) mmol/L, (50.3±22.3) vs (61.8±20.4) ng/ml, (17.1±6.7) vs (21.6±7.2) ng/ml; all P<0.05]. (3)The overall vitamin D deficiency rate during the third trimester of the four groups was 78.6% (110/140), and the figure was 62.8% (22/35), 82.8% (29/35), 77.1% (27/35) and 91.4% (32/35) in the NW-control group, OW-control group, NW-GDM group and OW-GDM group (χ2=8.994, P=0.029), indicating a higher rate in the OW-GDM group than that in the NW-control group (χ2=8.102, P=0.004). (4) VDR was expressed in the nucleus of adipose tissue in all samples and statistic difference in protein expression was found among the four groups. VDR mRNA expression was higher in both GDM subgroups than that in the two control subgroups, and also higher in the two overweight/obese subgroups than in the corresponding normal-weight subgroups. (5)Serum vitamin D level was negatively correlated with fasting blood glucose and pre-pregnancy BMI, and positively correlated with adiponectin (P<0.05). The incidence of GDM was related to family history of diabetes, VDR mRNA, total cholesterol, HDL-C and HOMA-IR. ConcLusions GDM and overweight/obese patients had decreased serum vitamin D level and increased VDR in subcutaneous adipose tissue. These two factors are closely related to GDM.

The role of inadequate vitamin D receptor activation and CYP27B1 metabolic modulation in the cardiorenal syndrome / 天津医药

@#In recent years, it has been found that the lack of vitamin D receptor (VDR) activation is closely associated with the development of cardiorenal syndrome (CRS). Hydroxylation catalyzed by renal 25-hydroxyvitamin D-1α hydroxylase (CYP27B1) is responsible for over 90% circulating concentrations of vitamin D activation, which then exerts biologic actions of vitamin D. Loss of renal CYP27B1 during CRS is associated with gradual decline in circulating 1,25(OH)2D3, resulting in inadequate VDR activation in renal and cardiac tissues, thereby promoting renal and cardiac damages. Therefore, CYP27B1 and VDR may become key targets for the combination of chronic kidney disease and cardiovascular disease. In this paper, the roles of vitamin D/VDR and metabolic regulation of CYP27B1 in CRS are reviewed, which may also provide new therapeutic strategies for CRS.

Studies on the relationship of vitamin D receptor gene distribution and bone mineral density in patients with maintenance peritoneal dialysis / 中国医师杂志

Objective To explore frequency distribution of vitamin D receptor (VDR) genotype and the correlations between polymorphism of VDR gene Bsm Ⅰ sites and bone mineral density in the patients undergoing maintenance peritoneal dialysis.Methods A case-control study was conducted based on 82 patients with maintenance peritoneal dialysis and 80 healthy people.The frequency distribution of VDR genotype in two groups was detected and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Serum biochemistry and bone mineral density of the patients undergoing maintenance peritoneal dialysis were detected by dual energy X-ray absorption (DEXA) and automatic biochemical analyzer,respectively.All data was analyzed with SPSS 19.0 software.Results The frequency distribution of VDR genotype between case group and control group had no significant difference (P ＞ 0.05).The serum biochemical index such as Ca,P,alkaline phosphatase (ALP) and parathyroid hormone (PTH)] of patients with maintenance peritoneal dialysis had no significant difference among three VDR genotypes(P ＞0.05).Compared to VDR bb genotype,the serum Ca was significantly higher in VDR BB genotype (P ＜0.05).The bone mineral density (BMD) and T-Score of patients with VDR BB genotype were the lowest,the BB genotype was the highest,and the difference was statistically significant among three genotypes (P ＜0.05).Conclusions The frequency distribution of VDR genotype between case group and control group had no significant difference.However,there is a correlation between VDR gene BsmⅠ sites and bone mineral density of maintenance peritoneal dialysis patients.

Expressions of serum 25 (OH)D, vitamin D receptor and vitamin Dl-α hydroxylase in intestinal mucosa tissues of patients with inflammatory bowel disease / 中华消化杂志

Objective To investigate the expression of serum 25(OH)D,vitamin D receptor (VDR)and vitamin D1-α hydroxylase (CYP27B1) in intestinal mucosa tissues of patients with inflammatory bowel disease (IBD).Methods From January 1st to December 31st in 2014,105 patients with IBD were enrolled,among them there were 49 cases of ulcerative colitis (UC) and 56 cases of Crohn's disease (CD);there were 20 cases in remission,26 cases in mild active phase,37 cases in moderate active phase and 22 cases in severe active phase;and 50 cases with lesions located in the left colon and 55 cases with lesions located in the right colon.At the same period,45 healthy individuals were also recruited as controls,whom were suspected as IBD but at last proved healthy.The lactulose and mannitol absorption ratio (LMR),serum endotoxin,tumor necrosis factor-α (TNF-α) and 25(OH)D levels,and the expressions of VDR and CYP27B1 in the intestinal mucosa tissues were detected in all the subjects.T test,one-way analysis of variance and chi square test were used for statistical analysis.Results The LMR,endotoxin and TNF-α levels of UC group were (63.2 ± 13.9)％,(118.9 ± 19.7) EU/mL,and (109.6 ± 18.4) ng/L,respectively,which were higher than those of the healthy control group ((3.3 ± 1.2)％,(34.2 ±5.6) EU/mL,and (0.6±0.3) ng/L);the level of 25 (OH)D was (36.6± 9.7) nmol/L,which was lower than that of healthy control group ((49.6± 10.9) nmol/L),and all the differences were statistically significant (t =28.796,29.284,27.817 and 6.118,all P＜0.05).LMR,endotoxin and TNF-α levels of CD group were (52.9±11.3)％,(96.4±10.6) EU/mL and (83.0±16.1) ng/L,respectively,which were higher than those of the healthy control group,25(OH)D level was (44.4±9.4) nmol/L,which was lower than that of healthy control group,and all the differences were statistically significant (t=34.555,39.716,34.293 and 0.012,all P＜0.05).The differences in LMR,endotoxin,TNF-α and 25 (OH)D levels among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=286.731,385.690,657.830 and 18.932,all P＜0.01) which was dependent on the disease activity.Compared with those of the healthy controls,the levels of LMR,endotoxin and TNF-α of the left colon group and the right colon group increased,and 25(OH)D levels decreased.The high expression rates of VDR in UC group and CD group were 36.7％ (18/49) and 55.4％ (31/ 56),respectively,which were both lower than that of healthy control group (80.0％ (36/45)),and the differences were statistically significant (x2 =38.574 and 13.837,both P＜0.05).The high expression rates of CYP27B1 of UC group and CD group were 26.5％ (13/49) and 35.7％ (20/56),respectively,which were both higher than that of healthy control group (22.2％ (10/45)),and the differences were statistically significant (x2=6.499 and 4.430,both P＜0.05).The differences in the high expression rates of VDR and CYP27B1 among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=33.470 and 27.142,both P＜0.01),which was dependent on the disease activity.Compared with that of the healthy control group,the high expression rates of VDR of the left colon group and the right colon group decreased,and the high expression rates of CYP27B1 increased.Conclusion There is vitamin D metabolic imbalance in IBD patients,as well as low serum 25(OH)D level,low rate of high VDR expression in colonic mucosa tissues and high rate of high CYP27B1.

The distribution of vitamin D receptor gene polymorphisms in patients with chronic obstructive pulmonary disease in Changsha / 中国医师杂志

Objective To investigate the genetic predisposing factor of chronic obstructive pulmonary disease (COPD) by studying the distribution of vitamin D receptor (VDR) gene polymorphisms in patients with COPD in Changsha.Methods Totally 120 COPD patients and 120 volunteers were enrolled in the study.Polymorphisms of VDR genes including Apa I and Bsm I were detected with polymerase chain reaction-restriction fragments length polymorphism (RFLP).Results There existed statistical difference in polymorphism of Apa I gene and frequency of distribution on its allele between two groups (P ＜ 0.05),while there is no significant difference on Bsm I gene between the two groups (P ＞ 0.05).Conclusions COPD is associated with the polymorphism of VDR-Apa I.There may be no relationship on VDR-Bsm I between two groups.

Association of vitamin D receptor polymorphisms with susceptibility to psoriasis vulgaris and clinical response to calcipotriol in patients with psoriasis vulgaris / 中华皮肤科杂志

Objective To investigate association of vitamin D receptor (VDR) polymorphisms with susceptibility to psoriasis vulgaris and clinical response to calcipotriol in patients with psoriasis vulgaris.Methods A total of 110 patients with psoriasis vulgaris and 183 healthy controls were enrolled into this study,and they were all of Han nationality from Hainan province.Ligase detection reaction (LDR) was conducted to determine the genotypes of VDR gene polymorphisms rs2228570,rs731236,rs1544410 and rs7975232.Single nucleotide polymorphism (SNP)-based association analysis in genotypic and allelic models,and haplotype-based association analysis were then performed.Then,75 patients with psoriasis area and severity index (PASI) scores less than 10 were topically treated with calcipotriol ointment alone.After 6-week treatment,the efficacy of calcipotriol ointment was evaluated,and the correlation between the efficacy and individual genotypes was analyzed.Results The frequency of A allele of rs7975232 in the psoriasis group and control group was 39.09％ and 27.05％ respectively,and the risk of developing psoriasis in rs7975232 A allele carriers was significantly higher than that in non-carriers (OR =1.731,95％ CI:1.213-2.471,P ＜ 0.05).Additionally,the risk of developing psoriasis in individuals with AA genotype (OR =2.404,95％ CI:1.085-5.328,P ＜ 0.05),as well as in individuals with AC genotype (OR =2.143,95％ CI:1.283-3.579,P ＜ 0.05),was significantly higher than that in patients with CC genotype.CTGA haplotype carriers (rs2228570,rs731236,rs1544410,rs7975232,respectively) had significantly higher risk of developing psoriasis compared with non-carriers (OR =1.907,95％ CI:1.132-3.214,P ＜ 0.05).Among 72 patients with mild-to-moderate psoriasis whose PASI scores were less than 10,patients with CC genotype of rs7975232 showed better response to calcipotriol ointment compared with those with AC genotype (OR =3.798,95％ CI:1.061-13.590,P ＜ 0.05) and those with AA genotype (OR =9.667,95％CI:1.556-60.040,P ＜ 0.05).Conclusion VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in patients with psoriasis individuals.

Bufalin alleviates adriamycin-induced podocyte injury by up-regulating the expression of vitamin D receptor / 中华肾脏病杂志

Objective To investigate the role of vitamin D receptor (VDR) in the protection of bufalin on podocyte injury induced by adriamycin (ADR).Methods (1) In vitro:the toxic effect of different concentrations of bufalin (10-9,10-8,10-7,104 mol/L) on podocyte was evaluated by lactate dehydrogenase (LDH) test;Annexin V-FITC and RT-PCR were utilized for podocyte apoptosis and VDR mRNA level respectively.Western blotting was used to analyze the protein expression of VDR and nephrin.SiRNA intervene was also applied to evaluate the role of VDR in bufalin's protective effect on podocyte injury induced by ADR.(2) In vitro:24 SD rats were randomly divided into three groups:control group,ADR group and ADR+bufalin group.TUNEL assay was applied to detect the apoptosis of podocytes in the kidney.Immunofluorescence and transmission electron microscope (TEM) were applied to analyze the expression of VDR and the ultrastructure of the glomerulus.Results Bufalin concentration lower than 10-7 mol/L had no toxicity on normal podocyte.Bufalin reduced the urinary protein excretion (P ＜ 0.05),alleviated the removal of podocyte foot processes and attenuated the changes in nephrin expression in the glomerulus of the adriamycin (ADR) rats (P ＜ 0.05).Bufalin notably inhibited the down-regulation of VDR in protein levels on the glomerulus of the ADR rats.Additionally,bufalin inhibited the down-regulation of VDR in both mRNA levels and protein levels (P ＜ 0.05),nephrin protein expression (P＜ 0.05),and apoptosis induced by ADR in cultured podocytes.Additionally,VDR specific siRNA intervene abolished the protective effect of bufalin in ADR-induced podocyte injury.Conclusion Bufalin can alleviate ADR-induced podocyte injury via enhancing VDR expression.

Association between Bsm1 Polymorphism in Vitamin D Receptor Gene and Diabetic Retinopathy of Type 2 Diabetes in Korean Population

BACKGROUND: Type 2 diabetes is one of the most common diseases with devastating complications. However, genetic susceptibility of diabetic complications has not been clarified. The vitamin D endocrine system is related with calcification and lipolysis, insulin secretion, and may be associated with many complicated disease including diabetes and cardiovascular disease. Recent studies reported that single nucleotide polymorphisms of vitamin D receptor (VDR) gene were associated with diabetic complications. METHODS: In present study, we evaluated the association of BsmI polymorphism of VDR with diabetic complications in Korean diabetes patients. Total of 537 type 2 diabetic subjects from the Endocrinology Clinic of Chungbuk National University Hospital were investigated. Polymerase chain reaction-restriction fragment length polymorphism was used to test the genotype and allele frequency of BsmI (rs1544410; BB, Bb, bb) polymorphisms. RESULTS: Mean age was 62.44+/-10.64 years and mean disease duration was 13.65+/-7.39 years. Patients with B allele (BB or Bb) was significantly associated with lower risk of diabetic retinopathy (severe non-proliferative diabetic retinopathy or proliferative retinopathy; 7.4%, 5/68) compared with patients without B allele (bb; 17.3%, 81/469; P=0.035). This association was also significant after adjusting for hemoglobin A1c level, body mass index, age, sex, and diabetes mellitus duration, concurrent dyslipidemia and hypertension (odds ratio, 2.99; 95% confidence interval, 1.08 to 8.29; P=0.035) in logistic regression analysis. CONCLUSION: Our findings suggest that B allele of Bsm1 polymorphism in VDR gene is associated with lower risk of diabetic retinopathy in type 2 diabetic patients. Bsm1 genotype could be used as a susceptibility marker to predict the risk of diabetes complication.

The correlations between vitamin D receptor FokⅠpolymorphism and type 2 diabetes in postmenopausal women / 实用医学杂志

Objective To study the correlations of VDR FokⅠgene polymorphism with type 2 diabetes in postmenopausal women of Han nationality in south Sichuan. Methods 160 patients with type 2 diabetes (T2DM) and 190 healthy cases were enrolled in the study. The VDR FokⅠgene polymorphisms were detected using RFLP-PCR and DNA sequencing. Results The FF, Ff and ff genotype frequencies were 32.5%, 47.5%and 20% in the T2DM group and 15.8%, 53.7%, 30.5% in the control group, respectively (P < 0.05). The allele frequencies were 56.3%, 43.8% in the T2DM group and 42.6%, 57.4% in the control group, respectively (P < 0.05). The risk of T2DM in the FF genotype people was 2.568 times higher than Ff/ff genotype (adjusted OR = 2.568, 95%CI = 1.246 ~ 5.292, P < 0.05). The levels of 2 h PG and HbA1C in the FF genotype people were significantly higher than those of the Ff/ff genotype people (P<0.05). Conclusions There was an association between the VDR FokⅠgene polymorphism and type 2 diabetes incidence in the postmenopausal women in south Sichuan area.

Serum level of vitamin D3 in cutaneous melanoma / Nível sérico de vitamina D3 em portadores de melanoma cutâneo

Objective To compare the level of vitamin D3 in cutaneous melanoma patients, with or without disease activity, with reference values and with patients from a general hospital. Methods The serum levels of vitamin D3 were measured in cutaneous melanoma patients, aged 20 to 88 years, both genders, from January 2010 to December 2013. The samples from the general group were processed at Hospital Israelita Albert Einstein (control group). Data analysis was performed using the Statistics software. Results A total of 100 patients were studied, 54 of them men, with mean age of 54.67 years, and 95 Caucasian. Out of these 100 patients, 17 had active disease. The average levels of vitamin D3 in the melanoma patients were lower than the level considered sufficient, but above the average of the control group. Both groups (with or without active disease) of patients showed a similar distribution of vitamin D3 deficiency. Conclusion Vitamin D3 levels in melanoma patients were higher than those of general patients and lower than the reference level. If the reference values are appropriate, a large part of the population had insufficient levels of vitamin D, including those with melanoma, or else, this standard needs to be reevaluated. No difference in vitamin D3 levels was found among melanoma patients with or without active disease. More comprehensive research is needed to assess the relation between vitamin D and melanoma. .

Objetivo Comparar o nível de vitamina D3 em portadores de melanoma, em atividade de doença ou não, com os valores de referência e com pacientes de um hospital geral. Métodos Os níveis séricos de vitamina D3 foram dosados em portadores de melanoma cutâneo entre 22 a 80 anos, de ambos os sexos, de janeiro de 2010 a dezembro de 2013. As amostras do grupo dos pacientes gerais foram processadas no Hospital Israelita Albert Einstein (grupo controle). A análise dos dados foi realizada utilizando o software Statistica. Resultados Foram estudados 100 pacientes, sendo 54 homens, com média de idade 54,67 anos, e 95 brancos. Desses 100 pacientes, 17 apresentavam doença em atividade. A média dos níveis de vitamina D3 nos 100 pacientes foi inferior ao nível considerado suficiente, porém acima da média do grupo controle. A deficiência de vitamina D3 apresentou distribuição semelhante nos dois grupos com melanoma (em atividade de doença ou não). Conclusão Os níveis de vitamina D3 nos pacientes com melanoma foram superiores aos dos pacientes gerais e inferiores aos de referência. Se os valores de referência estão adequados, grande parte da população apresenta níveis insuficientes de vitamina D3, incluindo os portadores de melanoma, ou tal padrão precisa ser reavaliado. Não houve diferença dos níveis de vitamina D3 entre portadores de melanoma com ou sem atividade. Estudos relacionando vitamina D e melanoma devem ser aprofundados. .

Effect of Carbonated Drinks on Primary and Permanent Teeth Replacement in Children / 天津医药

Objective To study the effect of carbonated drinks on primary and permanent teeth replacement in Chil-dren. Method Dog tooth enamel samples were soaked in coca-cola, sprite and pure soda, and the calcium, phosphorus lev-el were analysed. Dental papilla stem cells were separated and cultured in the conditioned medium by adding three drinks. PCR and western blot were used to detect mRNA and protein levels of activator of nuclear factor-k B receptor ligand (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR) , then the possible role of each gene and interactions rela-tionship were analyzed. Results Compared with saline, coca-cola and sprite showed their significantly decalcification and dephosphorization role, while plain soda water showed calcium and phosphorus protective effect. These three drinks had no effect on mRNA and protein levels of RANKL gene (P>0.05). Coca-cola and sprite can reduce OPG mRNA and protein lev-els, and at the same time increase transcription and expression of the VDR gene. Plain soda water has no effect on the OPG gene manifestation, but can significantly reduce the transcription and translation level of the VDR gene. Conclusion Car-bonated drinks may affect the dental health of the children's primary and permanent teeth replacement by regulating bone re-lated gene expression and vitamin D receptor family.

Functional Roles of 1,25(OH)2D3 in Osteogenic Differentiation of the Dental Papilla Stem Cells / 天津医药

Objective To study the functional roles of 1,25(OH)2D3 in osteogenic differentiation of the dental papilla stem cells. Methods The dental papilla stem cells were isolated and cultured in medium supplemented with different con-centrations of 1,25(OH)2D3 (1, 10 and 100 nmol/L). MTT assay was used to detect the cell growth, and flow cytometry was used to detect the cell cycle. Western blot assay was used to detect protein expression levels of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG) and vitamin D receptor (VDR). After siRNA silencing VDR expression, protein levels of RANKL and OPG were detected. Results MTT and flow cytometry results showed that there were no sig-nificant differences in the cell proliferation between different concentrations of 1,25(OH)2D3 (1, 10 and 100 nmol/L) and con-trol groups (P>0.05). Western blot results showed that there were protein expressions of VDR, RANKL and OPG in control group. The protein expressions of VDR, RANKL and OPG were increased after adding 1,25(OH)2D3, in which the upward trend was the most significant in VDR. After VDR expression was silenced by siRNA, the protein expression levels of VDR, RANKL and OPG were decreased. Conclusion 1,25(OH) 2D3 affects the osteoblast differentiation process of the dental pa-pilla stem cells by adjusting the VDR expression.

Expression of Vitamin D Receptor by Pulse Consumption in the Uterus of Menopausal Mouse Model / 대한폐경학회지

OBJECTIVES: Phytoestrogen-containing pulse supplements have beneficial effects on postmenopausal symptoms, but how such effects are achieved is unclear. This study investigates the effects of pulse consumption on the menopausal changes in ovariectomized rats. METHODS: Female Sprague-Dawley rats were either sham operated (Sham; n = 3) or surgically ovariectomized (n = 13). The Sham group was fed the regular AIN-93M diet. Ovariectomized group was divided into 3 sub-groups and fed AIN-93M containing soybean (n = 5), mung bean (n = 3), or cowpea (n = 5) for 10 weeks. At the end of the experiment, all rats were sacrificed, and the uterus was harvested, rinsed, and weighed. Expressions of vitamin D receptor (VDR), estrogen receptor (ER) beta, and ezrin in uterus were evaluated by immunohistochemistry. RESULTS: VDR was highly expressed in the uterus of rat, irrespective of ovariectomized state. VDR was more definitely expressed in the uterus of ovariectomized groups than the sham-operated group. There were no significant differences in expression of ER beta. However the expression of ezrin was highly expressed in the cowpea group compared to sham group (P = 0.044). CONCLUSION: This study suggested that legumes diet may concern menopausal changes via VDR and ezrin. The result may partly explain the beneficial effects of VDR on menopausal symptoms. Further study is necessary to study the detailed mechanisms of VDR and ezrin on the menopausal changes in the uterus.

Association of vitamin D receptor gene BsmI polymorphisms with type 2 diabetic nephropathy / 中华肾脏病杂志

Objective To investigate the association between Bsml polymorphism in vitamin D receptor (VDR) gene and diabetic nephropathy in Chinese Han population. Methods PCR-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotype and allele frequency of Bsml in 304 patients with type 2 diabetes mellitus (DM group) and 100 healthy individuals (NC group).The DM group was further divided into non-diabetic nephropathy group (DN0 group,122 cases),minimal albuminuria group (DN1 group,87 cases),and mass albuminuria group (DN2 group,95 cases).Eighty-three DM patients without nephropathy for over 5 years were L-NDN subgroup,and 64 DM patients with nephropathy occurring within the first year were EDN subgroup. Results Genotype and allele frequency of BsmI polymorphism were significantly different between DM and NC group (x2=7.088,P=0.008;x2=5.865,P=0.015).BB+Bb genotype and B allele frequency were significantly higher in DN2 group than those in NC group (x2=14.287,P=0.000;x2=12.621,P=0.000) and DN0 group (x2=8.063,P=0.005;x2=8.173,P=0.004).BB+Bb genotype and B allele frequency were significantly higher in EDN group than those in L-NDN group (x2=7.228,P=0.007; x2=5.853,P=0.016).DN patients with allele B (BB and Bb genotypes)presented higher urinary albumin excretion rates compared with patients without allele B (bb genotype,P＜0.01).The genotype of BsmI was correlated with DN,and allele B was risk factor of DN occurrence and early onset (OR=2.004; OR=2.394). Conclusion VDR gene BsmI polymorphism is associated with DN,and the patients carrying allele B are more involved in mass albuminuria and eady onset of nephropathy.

Inhibition of Vitamin D Receptor Translocation by Cigarette Smoking Extracts / 결핵및호흡기질환

BACKGROUND: Vitamin D can translocate a vitamin D receptor (VDR) from the nucleus to the cell membranes. The meaning of this translocation is not elucidated in terms of a role in pathogenesis of chronic obstructive pulmonary disease (COPD) till now. VDR deficient mice are prone to develop emphysema, suggesting that abnormal function of VDR might influence a generation of COPD. The blood levels of vitamin D have known to be well correlated with that of lung function in patients with COPD, and smoking is the most important risk factor in development of COPD. This study was performed to investigate whether cigarette smoke extracts (CSE) can inhibit the translocation of VDR and whether mitogen activated protein kinases (MAPKs) are involved in this inhibition. METHODS: Human alveolar basal epithelial cell line (A549) was used in this study. 1,25-(OH2)D3 and/or MAPKs inhibitors and antioxidants were pre-incubated before stimulation with 10% CSE, and then nucleus and microsomal proteins were extracted for a Western blot of VDR. RESULTS: Five minutes treatment of 1,25-(OH2)D3 induced translocation of VDR from nucleus to microsomes by a dose-dependent manner. CSE inhibited 1,25-(OH2)D3-induced translocation of VDR in both concentrations of 10% and 20%. All MAPKs inhibitors did not suppress the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR. Quercetin suppressed the inhibitory effects of CSE on the 1,25-(OH2)D3-induced translocation of VDR, but not in n-acetylcysteine. CONCLUSION: CSE has an ability to inhibit vitamin D-induced VDR translocation, but MAPKs are not involved in this inhibition.

Análise do polimorfismo Fok1 do gene VDR em mulheres inférteis com endometriose / Analysis of VDR gene polymorphism Fok1 in infertile women with endometriosis

OBJETIVO: avaliar a frequência do polimorfismo Fok1 do gene do receptor da vitamina D (VDR) em mulheres inférteis com endometriose e Grupo Controle, e sua associação com a doença. MÉTODOS: estudo caso-controle que incluiu 147 mulheres inférteis com endometriose e 154 mulheres férteis sem endometriose como Controle. O polimorfismo Fok1 (rs10735810, T2C), que promove uma troca de T/C no éxon 2 do gene VDR, foi identificado por PCR-RFLP (análise de polimorfismos de fragmentos de restrição), que envolve a combinação de amplificação por PCR (reação em cadeia da polimerase) e digestão com endonuclease de restrição. O teste do χ2 foi utilizado para comparar as frequências dos genótipos e alelos entre os grupos. Todos os valores de p foram bicaudais, e o nível de significância considerado foi 0,05 (α<0,05). RESULTADOS: os genótipos TT, TC e CC do polimorfismo FokI do gene VDR apresentaram frequência de 44,2 por cento, 46,9 por cento e 8,9 por cento nas mulheres inférteis com endometriose e 41,6 por cento, 50 por cento e 8,4 por cento no Grupo Controle, e não apresentaram diferença significante quando comparados (p=0,8), mesmo quando as pacientes com endometriose foram subdivididas de acordo com o estadiamento da endometriose (p=0,3 para endometriose mínima e leve e p=0,2 para endometriose moderada e grave). Em relação aos alelos, T e C estavam presentes, respectivamente, em 67,6 por cento e 32,3 por cento das mulheres inférteis com endometriose (p=0,8), em 63,5 por cento e 36,5 por cento das mulheres com endometriose mínima/leve (p=0,5), em 72,5 por cento e 27,5 por cento das mulheres com endometriose moderada/grave (p=0,2), e em 66,6 por cento e 33,4 por cento das mulheres do Grupo Controle. Não foi observada diferença estatística significante na comparação entre nenhum dos grupos e o Grupo Controle...

PURPOSE: to evaluate the frequency of VDR gene polymorphism Fok1 in infertile women with endometriosis and Control and its relation to the disease. METHODS: a case-control study that included 147 infertile women with endometriosis and 154 fertile women without endometriosis as Control. Fok1 polymorphism (rs10735810, T2C), which promotes a T/C exchange in exon 2 of the VDR gene, was identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), that involves the combination of amplification by PCR and digestion with restriction endonuclease. The χ2 test was used to compare allele and genotype frequencies between groups. All p-values were two-tailed and a p-value < 0.05 was considered statistically significant. RESULTS: the TT, TC and CC genotype frequencies of VDR Fok1 polymorphism were 44.2 percent, 46.9 percent and 8.9 percent in infertile women with endometriosis and 41.6 percent, 50 percent and 8.4 percent in the Control Group. No significant difference was found (p=0.8), even when the patients were subdivided according to the stage of endometriosis (p=0.3 for minimal and mild endometriosis and p=0.2 for moderate and severe endometriosis). Alleles T and C were present, respectively, in 67.6 percent and 32.3 percent of infertile women with endometriosis (p=0.8), in 63.5 percent and 36.5 percent of women with minimal/mild endometriosis (p=0.5), in 72.5 percent and 27.5 percent of women with moderate/severe endometriosis (p=0.2), and in 66.6 percent and 33.4 percent of the Control Group. No statistically significant difference was found among any groups and the Control...

High fat diet influence on vitamin D receptor expression and endothelial nitric oxide synthase in apolipoprotein E-deficient mice / 中国医师杂志

Objective This study investigated high fat diet influence on the changes of vitamin D receptor (VDR) expression and endothelial nitric oxide synthase (eNOS) in apolipoprotein E-deficient(apoE-/-) mice.MethodsApoE-/- mice and C57BLP6J mice were divide into two groups (normal control and high fat diet),high fat diet group were feed high fat feedstuff.Plasma 25-(OH)D levels were determined by competitive protein binding radioimmunity,VDR expression were determined by immunofluorescence and reverse transcription-polymerase chain reaction.The levels of NO and eNOS were determined by nitrate reductase.ResultsCompared with normal control group,high fat diet caused more severe dam-age of atherosclerosis in wild type mice and apoE-/- mice.In apoE-/- mice,the levels of plasma 25-(OH)D were significantly decreased [(26.44±1.28) ng/mL,(22.68±2.07)ng/mL,(17.46±2.22)ng/mL,(15.88±0.97)ng/mL,P＜0.01],the expression of VDR protein and mRNA were significantly increased[VDR :0.244±0.088,0.346±0.132,0.547±0.128,0.768±0.162;VDRmRNA:0.228±0.083,0.375±0.103,0.451±0.117,0.597±0.131,P＜0.01],and the levels of NO and eNOS were significantly increased[NO:(39.74±4.81)μmol/L,(48.1±5.24 )μmol/L,(67.34±6.14 )μmol/L,(86.74±8.05)μmol/L;eNOS:(8.6±0.77 )U/L,(12.28±1.42)U/L,(15.96±0.92)U/L,(18.68±1.15)U/L,P＜0.01].These changes were more significantly in high fat diet group(P＜0.01).ConclusionsThere were abnormalities of plasma 25-(OH)D level,VDR expression and the level of NO and eNOS in apoE-/- mice.These changes were more significantly in high fat diet group.

Study on the association between vitamin D receptor gene polymorphism of ApaI and BsmI and vitamin D deficiency rickets / 中国医师杂志

ObjectiveTo study the distribution characters and linkage disequilibrium of vitamin D receptor(VDR) gene ApaI and BsmI polymorphism,and explore the genetic susceptibility of VDR and vitamin D deficiency rickets.MethodsVDR gene ApaI and BsmI polymorphisms were determined by PCRRFLP technology in 56 cases of rickets and 76 cases of normal children.The frequencies of the VDR genotype and allele were compared between the two groups.The software SHEsis was used to make linkage disequilibrium analysis.Results No significant difference was found in either the frequency distribution of VDR gene ApaI and BsmI polymorphism or allele of them between two groups; Two polymorphisms didn't show linkage disequilibrium and D' and r2 were 0.23 and 0.01,respectively.ConclusionsThe ApaI and BsmI polymorphism of VDR gene might be not associated with vitamin D deficiency rickets.Two polymorphisms didn't show linkage disequilibrium.

Vitamin D receptor gene polymorphisms of sporadic myasthenia gravis in 267 Chinese Han patients / 中华神经科杂志

Objective To explore the associations between vitamin D receptor ( VDR) Fok- Ⅰ and Apa- Ⅰ polymorphisms and myasthenia gravis (MG) in Chinese Han population.Methods Polymorphisms of VDR Fok- Ⅰ and Apa-Ⅰ were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.The frequencies of genotypes and hyplotypes were compared among 286 normal controls and 267 MG patients in different subgroups classified by gender,age of onset,presence of thymoma,and Osserman classification sat maximal severity in the follow-up.The association between the genotypes and maximal severity of MG and short-term glucocorticoid treatment were also investigated.Results There were no significant differences in frequencies of genotypes and hyplotypes of both Fok-Ⅰ and Apa-Ⅰ between MG group and control group,and among subgroups of MG.The Fok- Ⅰ showed no statistical difference between the patients with better and less improvement after short-term treatment of glucocorticoid.The frequency of Apa-Ⅰ alleles in the patients with better improvement (55/186,29.6% ) significantly differed from the less improved group ( 7/48,14.6%,OR = 2.46,95% CI 1.04-10.43,x2 = 4.400,P = 0.036).The patients with the genotype A A/Aa were more likely to improve better after the treatment(48/93,51.6%) than in the worse group(7/24,29.2%,OR =2.59,95% CI 0.98-14.60,x2 =3.858,P= 0.049).Conclusions Alleles and genotypes of VDR-Fok- Ⅰ and Apa-Ⅰ were not found to be related with MG onset and severity.MG patients with VDR-Apa-A allele may have better improvement short-term treatment of glucocorticoid.