Bone mineral density,body height,and vitamin D receptor gene polymorphism in middle‐aged men

BACKGROUND. Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.

AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four‐year controlled, randomized intervention trial in 140 middle‐aged Finnish men.

METHOD. The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)‐markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2–L4), femoral neck, and total proximal femur were measured with dual‐energy X‐ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate‐resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated.

RESULTS. At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P = 0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P = 0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P = 0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD.

CONCLUSIONS. The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.     

VDR和CTR基因多态性与河北汉族妇女骨密度关系研究

[目的研究维生素D受体(VDR)和降钙素受体(CTR)基因多态性与河北汉族妇女骨密度(BMD)的关系,探讨原发性骨质疏松症(OP)发病的分子机制。方法采用聚合酶链反应-限制性片段长度多态性分析(PCR RFLP)方法对60 名河北汉族妇女的VDR和CTR基因进行多态性分析,比较不同基因型各部位BMD值的差异。结果VDR Bb基因型者各部位BMD值低于bb型( P <0.05);CTR CC基因型者L1~L4BMD值有较TC基因型者降低趋势(0.05< P <0.1);复合基因型CCBb的BMD值最低。结论VDR Bb基因型与低值BMD有密切关系;复合基因型CCBb可作为预测中国汉族妇女OP的一项遗传标志。     

Vitamin D receptor genotypes are related to bone size and bone density in men

Three restriction fragment length polymorphisms in the vitamin D receptor gene have been associated with a low bone density in twin and female population studies, but no studies have been conducted exclusively in men. We studied 146 normal men aged 20–83 years. Bone density was measured in the spine, hip, whole body and forearm, and the Bsm polymorphism for the vitamin D receptor was detected by the polymerase chain reaction. Men with genotype BB tended to have a lower bone density at all but one site than the other genotypes. In the men ≤50 years of age bone density in the forearm was 7% lower in the BB than the Bb and bb groups ( P   =  0.030) but bone mineral content did not differ between the groups. Bone area was greater in the BB genotype at all sites. This was statistically significant in the forearm ( P   =  0.026). We conclude that BB genotype is associated with lower bone density in men, which may be due to larger bone size rather than reduced bone mass.     

运动联合碳酸钙维生素D对绝经早期女性骨标志物的影响

目的探讨运动联合碳酸钙维生素D在预防绝经早期女性骨质疏松的疗效观察。方法选择100例绝经早期女性,分为试验组和对照组各50例,分别进行X线骨密度(BMD)检测和3种骨标志物检测,作为基线。试验组给予碳酸钙维生素D3片口服,连续3、6、12、18个月后再次检测BMD和骨标志物,观察各指标的变化情况。结果绝经早期女性均存在较高的骨代谢转换率。运动联合碳酸钙维生素D治疗,可显著影响3种骨标志物的水平,3种骨标志物与BMD呈负相关,而且骨转换指标的改变优先于BMD。试验组3种骨标志物3个月内已发生变化,分别下降25%、12%、10%。在监测碳酸钙维生素D对骨标志物影响时,3种骨标志物各具有不同特点。Ⅰ型前胶原羧基端肽B特殊序列(β-CTX)在早期3个月内即可显著下降,6个月后基本变化不明显;Ⅰ型前胶原氨基端延长肽(P1NP)和N端骨钙素(N-MID)反应时间较长,在抗重吸收6个月后才有明显变化,1年后基本维持在一定水平,而BMD的改变则至少需要12个月以上。结论坚持运动和持续补充碳酸钙维生素D,能有效降低骨骼重吸收和改善维生素D水平,对绝经早期女性预防骨质疏松有重大意义。     

妊娠糖尿病患者的维生素D受体基因单核苷酸多态性研究

目的探讨维生素D受体基因单核苷酸多态性与妊娠糖尿病(GDM)发病的关系。方法按病例-对照设计的方法,选取GDM患者和健康妊娠对照各80例作为受试对象,采用全自动生化分析仪检测受试者体内血糖和肝功能等指标;应用聚合酶链反应-基因测序法对所有受试者维生素D受体基因上的rs1544410位点进行多态性分析。使用SPSS13.0进行t检验和χ2检验分析。结果两组人群的维生素D受体基因rs1544410的G/A等位基因频率比较差异有统计学意义(P<0.05)。Bb型基因型的空腹血糖水平高于bb型(P<0.05),两组的肝功能指标相比差异无统计学意义。结论维生素D受体基因rs1544410多态性位点与南京地区汉族妊娠糖尿病具有相关性。     

老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系

目的 调查老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系.方法 调查576例60～97岁老年男性吸烟等情况,按照是否吸烟分成吸烟组31例和非吸烟组545例.检测两组骨转换标志物[包括I型胶原羧基末端肽交联(CTX)、I型前胶原氨基端前肽(P1NP)和骨钙素(OC)]、骨密度[包括股骨颈骨密度(FNBMD)...     

重庆地区骨质疏松患者25-羟维生素D与骨代谢的相关性分析

目的对25-羟维生素D和甲状旁腺激素(PTH)、N端骨钙素(N-MID)、降钙素(CT)、骨碱性磷酸酶(BALP)的相关性进行统计学分析,并探讨其在临床疾病的诊断、预防及治疗中的应用价值。方法收集2014年1-9月重庆医科大学附属第二医院住院患者411例,其中女316例,男95例;平均(69.29±12.21)岁。采用免疫电化学发光法检测住院患者25-羟维生素D、PTH、N-MID、CT、BALP的水平,探讨骨质疏松患者25-羟维生素D与骨代谢标志物的关系。结果25-羟维生素D与PTH、BALP均呈负相关关系(P0.05),而与CT、N-MID则无显著相关(P0.05)。回归分析显示,25-羟维生素D与骨代谢标志物回归方程为Y=19.02-0.066PTH-0.09BALP。结论骨质疏松患者25-羟维生素D水平的升高、降低与PTH、BALP均有一定相关性,通过对这些指标的检测,可以为临床骨质疏松患者的诊断、预防和控制提供基础数据。     

运动与活性维生素D联合作用对老年骨质疏松症患者骨量的影响

目的 探讨运动与活性维生素D联合作用对老年骨质疏松症患者骨量的影响。方法 将89例确诊为老年骨质疏松症患者随机分为2组：阿法骨化醇(α—D3)治疗组(A组，45例)和运动联合阿法骨化醇治疗组(B组，44例)。2组患者每人每天服用元素钙600mg、α—D3 0．25μg，B组患者同时进行有规律的运动训练。结果 单纯α-D3治疗后腰椎BMD明显上升，骨形成指标BGP水平明显升高，但骨吸收指标Pyd／Cr变化不明显；而联合治疗使腰椎和髋部的BMD均明显增加，并且骨形成指标BGP水平明显升高，骨吸收指标Pyd／Cr明显下降。结论 α-D，在促进老年骨质疏松症患者骨形成方面优于抑制骨吸收，对提高腰椎骨量具有优势。有氧运动联合α-D，不仅能增加老年骨质疏松症患者腰椎和股骨近端的骨量，同时能促进骨形成和抑制骨吸收，有效治疗老年人骨质疏松症，积极预防跌倒和骨折。     

Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor

First, the general structure and function of nuclear receptors (NRs) are described briefly to help our understanding of the mechanism of action of vitamin D mediated by the vitamin D receptor (VDR), a member of the NRs. Then we discuss the structure-function relationship (SFR) of vitamin D on the basis of ligand structures and the interaction of the ligand with the VDR. The SFR of vitamin D side chain analogs is discussed extensively in terms of our active space group concept, which was derived from conformational analyses of the side chains of vitamin D analogs and from studies with conformationally restricted 22-methyl-1,25-(OH)(2)D(3) isomers. The mobile area of the side chain of vitamin D can be grouped into five regions (E, G, EA, EG, and F), and the SFR has been analyzed in terms of these spatial regions. The SFR of ligand/VDR interaction is discussed on the basis of the crystal structure of VDR-LBD(delta 165-215), docking of various vitamin D ligands into the ligand binding pocket (LBP) of the VDR, and functional analysis of amino acids lining the LBP. Finally, we discuss total SFR, combining the results of the two approaches, and future aspects of structure-based design of vitamin D analogs.     

The clinical significance of vitamin D levels and vitamin D receptor mRNA expression in colorectal neoplasms

Background/AimThis study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development.MethodsPlasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme‐linked immunosorbent assay (ELISA) and real‐time fluorescence quantitative polymerase chain reaction (RT‐qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients.ResultsVitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para‐cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively.ConclusionsThe 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.     

Ethnic,geographic, and seasonal differences of vitamin D status among adults in south-west China

BackgroundThere are limited data on vitamin D status of Sichuan province, and no investigation has been carried out on the correlations of 25(OH)D and BTMs between healthy Hans and Tibetans of Sichuan province. This study aimed to examine 25(OH)D levels around Sichuan province and to assess differences by ethnicity, age, gender, sunlight exposure, geographic location, and seasons.MethodsBlood samples from 2317 healthy adults aged of 18 to 75 years and of Han and Tibetan ethnicities were collected in six regions and during four seasons. Serum 25(OH)D₂ and 25(OH)D₃ levels were measured by LC‐MS/MS method. Serum total P1NP and β‐CTX were measured by immunoassay.ResultsParticipants aged 18‐40 years showed significantly lower 25(OH)D levels than participants aged 41‐75 years old (P < .0001). The median serum 25(OH)D level for males was significantly higher than that of females (P < .0001). Serum 25(OH)D levels among four seasons and different districts varied significantly (P < .0001). In addition, the 25(OH)D level of Tibetans was significantly lower than that of Hans, while the serum total P1NP and β‐CTX levels of Tibetans were significantly higher than those of Hans (P < .0001).ConclusionAdult population was more common to have vitamin D deficiency/insufficiency among Tibetans, females, north regions and in spring and winter.     

甲状旁腺素、维生素D受体、雌激素受体基因多态对糖尿病患者骨密度的影响

目的探讨甲状旁腺素(PTH)基因多态与中国北方汉族人糖尿病患者骨密度的关系。分析维生素D受体(VDR)、雌激素受体(ER)基因多态性对PTH基因多态性与骨密度、骨量减少及骨质疏松关系的影响。方法运用PCR-RFLP技术检测1型糖尿病(T1DM)组54例、2型糖尿病(T2DM)组104例、健康对照(CON)组102例的中国北方汉族人PTH基因多态性。结果甲状旁腺素基因型和等位基因分布频率在T1DM组、T2DM组与CON组间差异无统计学意义(P0.05);DM患者Bb/bb基因型者发生骨量减少/骨质疏松的相对危险度增加(OR=2.8684)。联合VDR基因多态分析,Bbaa基因型组糖尿病患者并发骨量减少/骨质疏松的相对危险度增高(OR=4.3125);联合ER基因多态分析,bPxx基因型骨量减少/骨质疏松的相对危险度也增高(OR=4.0);联合分析PTH、VDR、ER基因型,同时存在3个或4个易感基因型者伴有骨量减少或骨质疏松,相对危险度增加(OR=5.5385)。结论糖尿病患者PTH基因多态性(BST B1位点)可能是预测骨量减少、骨质疏松易感性的遗传标志。联合VDR、ER基因多态有助于识别DM患者发生骨质疏松的高危人群。     

Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis

With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 +/- 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single-photonabsorptiometry on the distal non-dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25-hydroxy-vitamin D as well as 2-h-urinary-OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P less than 0.004; QCT: P less than 0.0001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P less than 0.012), urinary OH proline (P less than 0.05) and urinary calcium excretion (P less than 0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r = 0.32; P less than 0.04) in the osteoporotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.     

The vitamin D receptor Fok1 polymorphism and bone mineral density in Chinese children

BACKGROUND: To evaluate the relationship between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) in 213 healthy children aged 6-10 year in China. METHODS: A questionnaire survey of dietary pattern, outdoor activity was conducted among 213 children (boys 126, girls 86) randomly selected in Xishui county of Hubei province. The BMD was determined by dual energy X-ray absorptiometry at the distal forearm, calcium, phosphorus, and alkaline phosphatase in serum were immediately analyzed. The FokI polymorphism was detected by using PCR-RFLP. RESULTS: BMD was significantly higher in boys than in girls in 8/9 year group. (2) the frequencies of FF, Ff, and ff genotype were 25.8%, 62.0% and 12.2%, respectively; no difference was found between boys and girls. (3) BMD of children carrying FF genotype was higher (0.256+/-0.03) than those of carrying Ff genotype (0.241+/-0.03), P<0.01; the Ff genotype was associated with lowest forearm BMD in both boys and girls. Outdoor activity also positively affected peak bone mass. CONCLUSION: The Fok1 polymorphism of the VDR receptor seems to directly affect bone mineral mass in Chinese children.     

Association of vitamin D receptor genetic variants with bone mineral density and inflammatory markers in rheumatoid arthritis

Background and aimsVitamin D receptor (VDR) genetic variants are considered to have a role in the pathogenesis of rheumatoid arthritis (RA). This study examines an association of FokI, BsmI, ApaI and TaqI with RA, as well as with bone mineral density (RA with normal bone mineral density, RA-NBMD; RA with associated osteopenia, RA-OSTP; and RA with associated osteoporosis, RA-OP) and inflammatory markers.Materials and methodsVDR genetic variants were tested in 248 subjects using the PCR-RFLP method.ResultsSignificant differences were observed in the distribution of FokI genotypes between RA patients (p < 0.001), or subgroups (RA-NBMD, RA-OSTP, RA-OP) (p = 0.035, p = 0.02, p < 0.001, respectively) and controls. Prevalence of FokI f allele was significantly higher in RA group (p < 0.001) and subgroups (p = 0.003, p = 0.021, p < 0.001, respectively) compared to controls. An increased susceptibility to RA-OSTP was revealed in BsmI/ApaI Ba (AC) haplotype carriers (p = 0.012). A significantly higher erythrocyte sedimentation rate values were obtained in FokI FF compared to Ff + ff carriers (54.57 ± 23.73 vs. 22.83 ± 12.42; p < 0.001) within the RA-NBMD subgroup.ConclusionThe results of the study indicate an association of RA with FokI genetic variant and increased susceptibility to RA in f allele carriers, as well as to RA-OSTP in BsmI/ApaI Ba (AC) haplotype carriers.     

维生素D受体基因多态性与系统性红斑狼疮研究进展

近年来人们对常见病的高危因素集中在基因研究方面,研究显示维生素D受体(VDR)存在多态性,但是VDR基因多态性对VDR蛋白质功能和信号通路的影响还不明确。目前,数个毗邻的限制性片段长度多态性如BsmI、ApaI、TaqI、FokI等与疾病的联系受到广泛关注,而VDR基因多态性的作用机理在自身免疫性疾病系统性红斑狼疮(systemic lupus erythematosus,SLE)、糖尿病及骨关节炎等方面知之甚少。本文就VDR多态性与SLE发病机制的研究及其进展进行综述。     

The relationship between vitamin D receptor gene and TREM‐1 gene polymorphisms and the susceptibility and prognosis of neonatal sepsis

ObjectiveThe objective of this was to study the relationship between vitamin D receptor (VDR) and triggering receptor expressed on myeloid cells 1 (TREM‐1) gene single‐nucleotide polymorphisms (SNP) and neonatal sepsis susceptibility and prognosis.MethodsThe blood of 150 neonatal sepsis patients and 150 normal neonates was collected, and genomic DNA was extracted. Sanger sequencing was used to analyze the genotypes of VDR rs739837 and TREM‐1 rs2234246.ResultsVitamin D receptor rs739837 locus GT, TT genotype, dominant model, and recessive model were all protective factors for sepsis (0 < OR < 1, p < 0.05). The risk of sepsis in carriers of the rs739837 G allele was 0.65 times that of the rs739837 T allele (95% CI: 0.50–0.83, p < 0.001), CT, TT, dominant model, and recessive model at rs2234246 were risk factors for sepsis (OR > 1, p < 0.05). The risk of sepsis in carriers of the rs739837 T allele was 1.38 times that of carriers of the C allele (95% CI: 1.16–1.61, p < 0.001). The polymorphisms of VDR gene rs739837 and TREM‐1 gene rs2234246 were not significantly correlated with the survival of patients with neonatal sepsis (p > 0.05).Conclusion Vitamin D receptor gene rs739837 locus G>T is associated with a reduction in the risk of neonatal sepsis, TREM‐1 rs2234246 C>T is associated with the increased risk of neonatal sepsis, but none of them was significantly associated with the prognosis of neonatal sepsis.     

Influence of vitamin D administration on bone ultrasound measurements in patients on anticonvulsant therapy

BACKGROUND: The objective of the study was to evaluate bone mass status (as measured by bone ultrasound) in patients on anticonvulsant therapy, and the influence that Vitamin D administration exerts over it. MATERIALS AND METHODS: We measured and compared the basal serum levels of 25(OH)D3, parathyroid hormone (PTH), and phalangeal bone ultrasound (Ad-SOS), in 30 adult patients who were taking anticonvulsant drugs, with a control group of similar age and sex. We then gave the patients a large oral dose of 3 mg (120.000 UI) of 25(OH)D3, and repeated the measurements after one month. RESULTS: Basal 25(OH)D3 and Ad-SOS values were significantly lower, and PTH values significantly higher (P< 0.0001 in all), in the patient group. The low Ad-SOS values for the patients were independent of the treatment, but directly related to basal 25(OH)D3 levels (r = 0.45, P<0.01). There was a negative association between PTH and 25(OH)D3 (r = -0.64, P<0.0001), and no correlation between PTH y Ad-SOS (r = -0.20, p NS). After ingestion of the large dose of the vitamin D, the patient group registered a significant (P<0.0001) increase in 25(OH)D3 levels, their Ad-SOS values increased (P<0.0001) nearly to the mean basal value of the control group, and PTH decreased significantly (P<0.0001). CONCLUSIONS: These findings justify the need to assure adequate vitamin D intake in patients being treated with anticonvulsants, independently of the treatment, age, sex, and activity status, in order to prevent osteomalacia.