维生素D受体基因型与骨密度

目的考察维生素D受体(VDR)基因多态性在我国汉族人群中的分布频率,分析VDR基因型与骨密度的关系.方法采用聚合酶链反应和限制性酶切技术检测100例绝经前健康妇女VDR基因多态性.应用双能X线骨密度仪检测受试者腰椎及髋部骨密度.结果VDR基因型分布频率为BB型4.0%,Bb型10.0%,bb型86.0%;而三种基因型受试者髋部及腰椎骨密度均表现出Bb＞bb＞BB,经F检验腰椎骨密度3基因型比较,P＜0.05,具有显著差异.结论绝经前妇女VDR基因型分布频率与西方及国内的一些报道不尽相同,且骨密度显示出Bb＞bb＞BB,亦与国内外一些研究结果不同.     

哈尔滨地区部分汉族人群维生素D受体Bsm I基因多态性与骨质疏松性骨折关系的研究

目的旨在了解哈尔滨地区部分汉族人群维生素D受体(VDR)BsmⅠ基因多态性与骨质疏松性骨折患者骨密度(BMD)的相关关系。方法98例研究对象按骨质疏松性骨折诊断标准分2组,骨量正常组:48人;骨质疏松性骨折组:50人。聚合酶链反应限制性片断长度多态性(PCR-RFLP)技术检测98例受试者VDRBsmⅠ基因型。测试受试者腰椎2～4(L2-4),股骨颈(Neck)、大转子(Troch)、Wards三角、桡骨远端(Radius)5个部位骨密度(BMD)。结果骨折组各部位骨密度均显著低于对照组各部位骨密度,差异具有显著性(P<0.01)。受试者VDR基因型未发现BB型,检出Bb型16人,占16.3%,bb型82人,占83.7%。b和B等位基因频率分别为91.8%、8.2%,Bb、bb两基因型在两组之间的分布无差异;VDR两基因型与各部位BMD之间,虽然在腰椎2～4、股骨颈、大转子和桡骨远端等4个部位Bb基因型比bb基因型的BMD高,但结果没有统计学意义。结论这组哈尔滨地区人群VDR基因型分布以bb型、Bb型为主,VDR基因BsmⅠ多态性与骨密度之间没有相关关系。     

老年男性维生素D受体基因多态性与骨密度关系的研究

目的研究维生素D受体(vitamin D receptor,VDR)基因多态性在老年男性中的分布, 并进一步研究其与骨密度的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR- RFLP)方法,分析145例老年男性的VDR基因型,同时用双能X线吸收法测定腰椎及髋部骨密度。结果 VDR基因型分别为BB,0．014;Bb,0．117;bb,0．869。骨质疏松组与非骨质疏松组之间VDR基因型分布频率的差异无显著性(P>0．05)。比较各基因型组的骨密度,bb组及 Bb组只有在股骨颈处显示出BMD均低于BB组,差异有显著性(P<0．05),其它部位,三个基因型组的BMD均差异无显著性(P>0．05)。结论老年男性VDR基因型分布频率与某些西方国家人群分布不同,其VDR基因型与骨密度无明显相关性。VDR基因可能不是我们所研究群体 BMD的主要遗传基因。     

雌激素受体α和维生素D受体基因多态性与哈尔滨地区绝经后妇女骨密度的关系

目的探讨哈尔滨市绝经后妇女雌激素受体α(ER-α)基因和维生素D受体(VDR)基因多态性与骨密度的关系。方法对哈尔滨市81例无亲缘关系汉族健康妇女进行PCR-RFLP测定ER-α基因PvuⅡ、XbaⅠ多态性和VDR基因BSMⅠ多态性,用双能X线吸收法测定骨密度(BMD)。结果本研究人群PP、Pp及pp基因型频率分别为13.6%、49.4%、37.0%;XX、Xx及xx基因型频率各为4.9%、40.7%、54.4%;BB、Bb及bb基因型频率各为0%、16.0%、84.0%,t检验分析各基因型与BMD值的关系显示:绝经后妇女中,雌激素受体基因型仅与腰椎骨密度有显著差异。维生素D受体基因型在股骨颈、大转子部位有显著差异。PvuⅡ多态性和BSMⅠ多态性共同作用对骨密度影响更大。结论雌激素受体、维生素D受体基因型分布频率均符合Hardy-Weinberg定律,并且与骨密度有一定的关联,尤其是基因与基因的共同作用与骨密度的关系更为密切。     

VDR基因多态性与维持性血液透析患者肾性骨营养不良的关系

目的通过研究维持性血液透析(MHD)患者维生素D受体(VDR)基因多态性的变化,了解VDR基因多态性与肾性骨营养不良之间的关系。方法选择2016年1月至2017年11月武汉市第五医院就诊的MHD患者200例,年龄40～65岁,采用双能X线吸收测量法(DEXA)测量VDR BB基因型、VDR Bb基因型、VDR bb基因型3种不同基因型的骨密度水平。应用DEXA对股骨颈骨密度进行测量,并调查患者的一般情况,采用Pearson检验进行相关性分析,了解VDR基因多态性与骨代谢指标之间的相关性。结果 VDR bb基因型骨密度Z-Score值低于VDR Bb基因型,VDR Bb基因型的骨密度Z-Score值低于VDR BB基因型,不同基因型的MHD患者骨密度Z-Score值之间的差异具有统计学意义(P 0.05); MHD患者低骨量的发生率和骨矿质缺乏的发生率分别约为30.0%和20.0%,VDR不同基因型的MHD患者低骨量及骨矿质缺乏的患病率差异具有统计学意义(P 0.05);VDR bb患者骨代谢指标(钙、磷、ALP、PTH)与VDR BB、VDR Bb比较,差异均有统计学意义(P 0.05); MHD患者的骨密度与体质量相关(r=-0.260,P 0.05),与年龄和身高无相关性。结论 MHD患者肾性骨营养不良受遗传因素的影响,VDR基因BsmI多态性影响骨代谢,VDR基因多态性可以作为肾性骨营养不良的预测因子,并对临床治疗提供参考依据。     

长春市汉族女性维生素D受体基因BsmⅠ和FokⅠ位点多态性与骨密度相关性研究

目的研究长春市35~85岁汉族女性维生素D受体(vitamin D receptor,VDR)基因Bsm Ⅰ、Fok Ⅰ位点的多态性,并分析其与骨密度(bone mineral density,BMD)的相关关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析Bsm Ⅰ和Fok Ⅰ酶切位点多态性,采用Hologic Discovery WA型骨密度仪检测腰椎正位(L1~4)BMD。将230例受试者分成绝经组和未绝经组,观察两组各基因型分布特征,应用SPSS 19.0软件对试验结果进行统计分析。结果在本研究人群中,Bsm Ⅰ位点基因型分布情况为bb占83.9%、Bb占12.6%、BB占3.5%,b等位基因频率高达90.2%,B等位基因频率为9.8%;Fok Ⅰ位点基因型分布情况为ff占18.3%、Ff占43.9%、FF占37.8%,f等位基因频率为40.2%,F等位基因频率为59.8%,两位点基因型分布均符合Hardy-Weinberg定律(χ2=1.283,P=0.125;χ2=0.96,P=0.342);未绝经组与绝经组各基因型分布组间差异无统计学意义(P0.05);Bsm Ⅰ位点在未绝经组和绝经组中各基因型BMD无差异(P0.05);Fok Ⅰ位点ff型BMD较FF型和Ff型低,但在未绝经组中差异无统计学意义(P0.05),绝经组中ff型与FF型比较,BMD差异有统计学意义(P0.05)。结论在本研究的230例35~85岁汉族女性人群中,Bsm Ⅰ位点基因型分布以bb型为主,b等位基因频率高达90.2%,各基因型骨密度无差异;Fok Ⅰ位点ff型有较低的BMD,但在未绝经组中差异无统计学意义,在绝经后女性中ff型与低BMD相关。     

广州汉族成年人维生素D受体基因分布及其与骨密度关系的研究

目的　了解中国广州地区人群VDR基因多态性的分布及其与骨密度的关系。方法　选取居住广州地区的汉族成年人 396例。应用PCR RFLP等生物学技术检测VDR基因 ,用双能X线骨密度仪 (DEXA)对入选的大部分对象进行了全身、腰推正侧位 ,股骨近端BMD检测。结果　VDR基因分布频率是BB 6 5 %、Bb 4 8 2 %、bb 4 5 3% ;本组对象峰值骨量出现在 30～ 39岁组 ,并且以Bb基因型的BMD值最高 ;3种基因型按BMD大小排列顺序为 :Bb >BB >bb ,但只有Bb与bb两基因型的BMD存在着差异。结论　①VDR基因多态性与种族、居住地区和人群不同有关。②峰值骨量出现在 30～39岁组 ,以Bb基因型对应较高的BMD ,bb基因型对应较低的BMD。③VDR基因型与BMD间存在着关联 ,但对其骨质疏松相对高危人群的预测价值有待进一步的深入研究。     

上海地区汉人维生素D受体基因多态性与骨密度关系的初步分析

目的：了解维生素D受体（VDR）基因多态性在中国人群中的分布，并进一步研究其与骨密度的关系。方法：通过聚合酶链反应－限制性片段长度多态性（PCR－RFLP）方法分析了348例无亲缘关系的上海地区男女居民的VDR基因型，并用双能X线吸收仪测定了其中202例骨密度。结果：348例研究对象中bb型占81．9％，Bb型占18．1％，未见到BB型。b等位基因在本组人群中分布 高达90．0％。男女性之间VDR基因型分布频率无明显区别（P＞0．5）。比较这两组各部位的骨密度值，只有女性在华氏三角区部位显示出Bb型比bb型有较高的BMD，在其余部位，不管男性还是女性，两组基因型的BMD均差异无显性（P＞0．05）。结论：VDR基因多态性与骨密度无相关关系。     

甲状旁腺素和维生素D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)基因多态性与中国北方汉族人糖尿病患者骨密度的关系,联合分析维生素D受体(VDR)基因和PTH基因多态性与骨密度的相关性。方法选自青岛市内分泌糖尿病医院1998年1月~2002年1月住院的糖尿病患者,运用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术检测了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,260例中国北方汉族人PTH基因多态性;采用双能X线吸收法骨密度仪(DEXA)测量骨密度。结果校正年龄和BMI后,1型糖尿病组腰椎、股骨颈骨密度低于对照组(P0.05);2型糖尿病组与对照组相比,骨密度差异无显著性(P0.05);甲状旁腺素(BSTB1位点)基因型和等位基因分布频率在1型糖尿病组、2型糖尿病组与对照组间差异无显著性(P0.05);在对照组及2型糖尿病组,BB基因型者腰椎(L2-4)和股骨颈部位骨密度显著高于Bb/bb基因型(P0.05);在1型糖尿病组,BB基因型仅腰椎L2-4部位骨密度高于Bb/bb基因型(P0.05);联合VDR基因多态(Apa I酶切位点)分析结果表明,Bbaa基因型在腰椎和股骨颈骨密度低于其他基因型(P0.05)。结论糖尿病患者PTH基因多态性(BSTB1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基因多态(Apa I酶切位点)有助于识别糖尿病患者发生骨质疏松的高危人群。     

我国四种民族维生素D受体基因多态性分布的研究

目的 维生素D受体（VDR）基因与骨密度和骨量密切相关。但是它在不同人群和种族中的分布仍有差异。本研究旨在分析中国汉族、维吾尔族、哈萨克族和蒙古族维生素D受体基因多态性分布。方法 应用聚合酶链反应限制性片长度多态性技术，分别对我国179名汉族、122名维吾尔族、63名哈萨克族和112名蒙古族健康绝经后妇女的VDR基因型进行分型，并计算其基因频率分布。结果 汉族、维吾尔族、哈萨克族和蒙古族绝经后妇女bb基因型频率分别为90．5％、69．67％、38．1％和50％，上述四种民族BB基因型频率分别为0％、4．1％、6．35％和4．46％，汉族与维吾尔族、哈萨克族和蒙古族之间VDR基因型频率分布比较，差异有非常显著性（P〈0．001），哈萨克族与欧美人种比较，VDR基因型相差不显著。结论 我国汉族与维吾尔族、哈萨克族和蒙古族之间VDR基因型多态性具有种族差异性，这种种族差异性与骨质疏松的相关性有待于进一步研究。     

Studies on the frequencies of vitamin D receptor gene polymorphism in postmenopausal women of Han and Kazak nationality in China

Polymorphyism of the vitamin D receptor (VDR) gene is reported to play a major role in variations of the genetic regulation of bone mass. The role of VDR polymorphisms within various ethnic populations is also undetermined. The purpose of the present study was to determine the frequencies of VDR genotypes in the Han and Kazak nationalities in China. We analyzed the polymorphism defined by the Bsm1 restriction enzyme using polymerase chain reaction-restriction fragment length polymorphism in 179 healthy postmenopausal Han women and 63 healthy postmenopausal Kazak women. The genotype frequencies of the VDR were calculated later using the Hardy-Weinberg equilibrium formula. The results showed that for women of Han nationality, the bb, Bb, and BB genotypes accounted for 90.5%, 9.5%, and 0%, respectively. In Kazak women, the respective frequencies were 38.1%, 55.56%, and 6.35%. We found that there was a significant difference between women of Han and Kazak nationality in terms of the frequency of distribution of VDR genotype (P < 0.001). There was a similar distribution of VDR genotypes in Kazak women to that seen for the Caucasian population of the USA. The results of the present study provide further evidence on the different pathogeny of osteoporosis in various ethnic groups.     

Genotypes and clinical aspects associated with bone mineral density in Argentine postmenopausal women

The aim of this study was to determine genotypes and clinical aspects associated with bone mineral density (BMD) in postmenopausal women from Córdoba, Argentina. Polymorphisms were assessed by RFLP-PCR technique using BsmI and FokI for vitamin D receptor gene (VDR) and XbaI and PvuII for estrogen receptor-alpha gene (ERalpha) as restrictases. Sixty-eight healthy, 54 osteopenic, and 64 osteoporotic postmenopausal women were recruited. Femoral neck and lumbar spine BMD were inversely correlated with age in the entire analyzed population. Height was lower in osteopenic and osteoporotic women as compared to healthy women (P < 0.05). Weight and body mass index (BMI) were the lowest in osteoporotic women (P < 0.01 versus healthy group). Serum procollagen type I Nterminal propeptide (PINP) was higher in osteoporotic women as compared to the other groups. Distribution of VDR and ERalpha genotypes was similar in the three groups. Genotype bb (VDR) was associated with low values of lumbar BMD in the healthy group (P < 0.05 versus genotype Bb), and with low values of femoral BMD (P < 0.05 versus genotype BB) in osteoporotic women. BB*Pp interaction was associated with the highest femoral neck BMD (P < 0.05), whereas the bb*xx interaction was associated with the lowest femoral neck BMD in the total population analyzed (P < 0.05). In conclusion, parameters such as age, height, weight, BMI, serum PINP, VDR genotypes, and interactions between VDR and ERalpha genotypes could be useful to predict a decrease in BMD in Argentine postmenopausal women.     

宁夏回、汉老年女性原发性骨质疏松症的维生素D受体基因多态性研究

目的 探讨宁夏地区回、汉老年女性原发性骨质疏松症（primary osteoporosis,PO）维生素D受体基因（vitamin D receptor, VDR）基因多态性分布。方法 应用聚合酶链反应限制性片段长度多肽性技术（polymerase chain reaction-restrictive fragment length polymorphism, PCR-RFLP）,从2015年至 2018年筛选宁夏医科大学总医院门诊及住院患者,收集119例汉族和111例回族原发性骨质疏松症妇女的血液样本并进行VDR基因型的分型检测,探讨宁夏回、汉VDR基因多态性是否存在差异。结果 111例患者的VDR受体基因型频率分布均符合Hardy-Weinberg定律,汉族和回族的女性骨质疏松症的bb 型占89.20%,68.21%。Bb基因型频率分别为8.79%和27.16%,BB基因型频率为0.00%和3.80%。宁夏回、汉女性原发性骨质疏松症中VDR基因型频率分布差异具有统计学意义（P<0.001）。结论 宁夏回、汉女性原发性骨质疏松症患者VDR基因多态性存在民族差异性,这种民族差异性与骨质疏松症的相关性有待于进一步研究。     

Correlation Between Vitamin D Receptor Genotypes and Bone Mineral Density in Japanese Patients with Osteoporosis

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI. Received: 22 September 1995 / Accepted: 24 September 1996     

VDR Genotype and Response to Etidronate Therapy in Late Postmenopausal Women

Twenty-four late postmenopausal women with osteoporosis were studied. The patients were separated in three subgroups according to the BsmI polymorphism of the vitamin D receptor (VDR) gene: BB (n= 8), Bb (n = 10) and bb (n = 6). They did not differ in age (mean ages were 66.0 years, 65.9 years and 63.9 years, respectively), years after menopause (18.7 years, 18.1 years and 18.4 years) or body weight (64.9 kg, 65.3 kg and 63.8 kg), the variables known to be associated with bone mineral density (BMD). The results show that the response to antiresorptive bisphosphonate therapy in combination with calcium supplementation is modified by VDR genotype. The lumbar spine BMD increased significantly faster in the BB and Bb groups (7.3% and 7.0%, respectively) compared with the bb group (2.5%) during 1 year of cyclic etidronate therapy (400 mg/day) and calcium supplementation (1000 mg/day). The biochemical marker of bone resorption (urinary hydroxyproline excretion) as well as the bone formation marker (serum levels of osteocalcin) decreased during the treatment. With respect to VDR genotype, a significantly higher decrease in osteocalcin level was observed in bb as compared with BB subjects. We conclude that the VDR genotype is involved in an individual’s response to cyclic etidronate therapy with calcium supplementation. Received: 12 December 1998 / Accepted: 18 March 1999     

Early and Late Postmenopausal Bone Loss is Associated with BsmI Vitamin D Receptor Gene Polymorphism in Japanese Women

To determine whether vitamin D receptor (VDR) gene polymorphisms are associated with bone mineral density (BMD) and bone loss in the Japanese population, VDR BsmI RFLPs were analyzed in 191 postmenopausal Japanese women by comparing B allele and b allele DNA sequences, and a point mutation was confirmed. We examined VDR BsmI restriction fragment length polymorphism (RFLP) with an amplification refractory mutation system (ARMS) using this point of mutation. The frequency of VDR BsmI alleles in the Japanese population was significantly different from that in whites. The bb genotype was identified in 79.6%, of the subjects, the Bb genotype in 19.3%, and the BB genotype was in only 1.1%. We find no significant differences in lumbar spine baseline BMD between the bb genotype and the Bb genotype. In both early and late postmenopausal periods, serial measurements of vertebral BMD revealed that subjects with the Bb genotype lost BMD faster than those with the bb genotype (P= 0.001). We conclude that there is a significant relationship between RFLPs of BsmI VDR and the annual rates of bone loss during early and late postmenopausal periods in the Japanese population. Received: 14 May 1997 / Accepted: 9 July 1998     

Vitamin D Receptor Gene Polymorphisms, Bone Mass, Bone Loss and Prevalence of Vertebral Fracture: Differences in Postmenopausal Women and Men

Bone mineral density (BMD), the major determinant of fracture risk, is under strong genetic control. Although polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass, the influence of VDR genotypes on osteoporosis remains controversial. Previous published studies have focused mainly on women, but the pattern of response in men has not been determined. Using the BsmI restriction enzyme, we studied the influence of the different VDR genotypes on bone mass, bone loss and the prevalence of vertebral fractures in a population-based sample of both sexes (n = 326). BMD was measured at the lumbar spine and femoral neck, with a 4-year interval, using dual-energy X-ray absorptiometry. Vertebral fractures were assessed by two lateral radiographs at the beginning and end of the study. The prevalence of the three possible VDR genotypes was similar to those in other Caucasian populations and no differences were found between men and women. Women with the favorable bb genotype showed significantly higher BMD values at the lumbar spine and femoral neck, and a positive rate of BMD change at the femoral neck compared with women with the BB and Bb genotypes. Moreover, women with the bb genotype showed a trend toward a lower prevalence and incidence of vertebral fractures (p= 0.07). We have not found any differences between VDR genotypes in men. In conclusion, VDR gene polymorphisms are related to bone mass and bone loss in women; also a trend in the prevalence of vertebral fractures was observed in postmenopausal women but not in men. Received: 8 June 1998 / Accepted: 7 December 1998