女性护骨素基因启动子区G209A与T245G多态性和骨密度及骨转换的关系

研究护骨素基因启动子区G209A与T245G多态性和女性骨密度及骨转换生化指标的关系，结果显示G209A与T245G多态性和骨密度及骨转换生化指标无关。     

2型糖尿病患者护骨素基因启动子区950T→C多态性与血管并发症的关系

目的探讨2型糖尿病患者护骨素（OPG）基因启动子区950T→C多态性与合并冠心病、脑血管病、视网膜病变的关系。方法采用聚合酶链反应-限制性片断长度多态性（PCR—RFLP）法检测OPG基因型。结果OPG基因启动子区950T→C多态性与糖尿病合并冠心病、脑血管病无明显相关性（P〉0．05）,而与视网膜病变相关,合并视网膜病变患者C等位基因比例显著高于无视网膜病变患者（x^2=4．696,P〈0．05）。结论C等位基因可能增加2型糖尿病并发视网膜病变的遗传易感性。     

绝经后妇女护骨素基因G1181C多态性与骨密度变化相关

目的　寻找护骨素基因(OPG)外显子中的单核苷酸多态性 (SNP),并分析其与绝经后妇女骨密度的关系。方法　在 205名绝经后妇女中,采用PCR和直接测序法确定OPG基因的SNP及基因型。应用双能X线骨密度仪测定腰椎和股骨颈骨密度 (BMD)。同时检测血清骨钙素 (BGP)、尿Ⅰ型胶原交联N端肽(NTx),以及血清护骨素(OPG)和核因子κB受体活化子配体 (RANKL)。结果　在OPG基因第一外显子中发现一个G1181C的SNP,该SNP的基因型频率分布依次为GG型占 0. 566、GC型 0. 346、CC型0. 088。去除年龄和体重的影响后,CC型的腰椎BMD明显高于GC和GG型 (P<0. 05),多元回归分析提示OPG基因型与绝经后妇女腰椎、股骨颈BMD相关 (P<0. 01)。Logistic回归分析显示OPG基因是绝经后妇女发生骨量减少和骨质疏松的独立危险因子,GG型发生骨量减少和骨质疏松的危险是CC型的 2. 83倍(P<0. 05)。结论　OPG基因的G1181C多态性与绝经后妇女BMD存在一定的关联,CC型对绝经后妇女腰椎BMD具有保护作用。     

护骨素基因多态性与老年男性骨质疏松症的关系

目的探讨护骨素（OPG）基因启动子区T950C单核苷酸多态性与老年男性骨质疏松症发生的关系。方法选择98例老年男性骨质疏松症患者和101例正常老年男性,利用聚合酶链反应—限制性片段长度多态性分析技术检测OPG T950C多态位点的基因型,分析比较两组之间OPG T950C位点基因型频率的差异。结果OPGT950C基因型频率分布符合Hardy-Weinberg平衡,OPG T950C位点CC基因型频率在老年男性骨质疏松症患者和正常老年男性之间具有统计学差异（P〈0.01）。结论OPG基因启动子区T950C位点多态性与老年男性骨质疏松症的发生有关,OPG C950C基因型可能是老年男性发生骨质疏松的遗传易感性指标。     

上海地区老年汉族人群护骨素基因T950C多态性与冠心病及其严重程度的相关性研究

目的探讨护骨素（osteoprotegerin,OPG）基因T950C位点基因多态性与冠心病（coronary artery dsease,CAD）及其严重程度的相关性。方法290例行冠状动脉造影患者根据造影结果,分为正常冠脉组102例和冠心病组188例。冠心病组根据病变冠脉病变支数,分为单支组57例、双支组50例、三支组68例、四支组13例;冠心病组再根据病史分为急性冠脉综合征（acute coronary syndrome,ACS）组133例和稳定型冠心病组55例。介质纯化法提取白细胞DNA,聚合酶链式反应（polymerase chain reaction,PCR）扩增包含护骨素T950C位点的DNA片段,连接酶检测反应（ligase detection reaction,LDR）检测PCR产物,识别多态性位点。结果在正常冠脉组和冠心病组之间,在正常冠脉组和ACS组之间,在ACS组和稳定型冠心病组之间,在正常冠脉组和不同病变冠脉数量组之间,护骨素基因T950C的各基因型频率和分布差别无统计意义;冠心病组CC基因型的Gensini评分要高于TT基因型的Gensini评分。结论研究中未发现护骨素基因T950C位点基因多态性与冠心病相关;T950C位点多态性与冠心病的严重程度有相关性,CC基因型的冠脉狭窄程度较TT基因型更严重。     

体脂比率与OPG基因启动子G209-A和T245-G多态性联合作用与骨质疏松症发生的关系

目的探讨护骨素(OPG)基因启动子区G209-A和T245-G多态性及其脂肪保护作用、联合作用对绝经后正常妇女和绝经后骨质疏松症妇女骨密度(BMD)的影响。方法随机抽取25个样本经SSCP-PCR法寻找异常迁移条带,再采用测序方法确定扩增区域中的单核苷酸点突变位点,最后采用PCR-限制性片段长度法(RFLP)对所有样本进行分析;双能X线吸收法测定BMD。结果73例绝经后骨质疏松症妇女和61例绝经后正常妇女OPG启动子扩增区中找到两个单核苷酸点突变多态性位点,G209-A和T245-G。分析显示这两个多态性位点基因型频率在两组实验对象中的分布均符合Hardy-Weinberg定律。G209-A和T245-G多态性位点单一基因型和复合基因型的分布在两组实验对象之间没有显著性差异(P>0.05)。对各单一基因型及其复合基因型的BMD分析显示:绝经后骨质疏松症妇女的腰椎和髋部BMD明显低于绝经后正常妇女,同时,绝经后骨质疏松症妇女的全身体脂比率也明显低于正常妇女。结论G209-A和T245-G多态性对绝经后骨质疏松症和绝经后正常妇女的骨量影响没有协同作用;单一的和复合的G209-A、T245-G多态性各基因型不能作为预测中国汉族妇女是否发生骨质疏松症的遗传标志,但可能是骨质疏松症发生的易感基因,并且合理的含脂饮食有利于骨保护。     

护骨素基因C1217T多态性对应用糖皮质激素患者骨量的影响

糖皮质激素（GO）在肾脏疾病、风湿性疾病、器官移植等领域应用广泛，其长程治疗相关的骨质疏松也逐渐成为肾科医师关注的重要问题。糖皮质激素性骨质疏松症的发病率仅次于绝经后及老年性骨质疏松症而居第三位。护骨素（OPG）是肿瘤坏死因子受体超家族成员之一，OPG基因是调节骨量的一个候选基因。我们对应用糖皮质激素患者OPG基因内含子C1217T单核苷酸多态性及其与骨量、骨代谢指标之间的相关性进行了研究。     

老年类风湿关节炎外周血护骨素表达水平及对骨密度的影响

目的检测老年类风湿关节炎患者外周血护骨素(OPG)的表达水平并分析其与骨密度的相关性。方法老年类风湿关节炎患者46例设为观察组,同期在我院健康体检的老年人46例为对照组。回顾性分析两组研究对象的临床资料,分析和比较两组骨密度以及OPG、核因子κB受体活化因子配基(RANKL)等血液学指标。结果观察组患者OPG水平显著低于对照组(P0.01),而肿瘤坏死因子(TNF)-α及RANKL水平显著高于对照组(P0.01)。观察组患者前臂、大转子、股骨颈及L1~L4四个部位骨密度值均显著低于对照组(P0.01),观察组患者骨密度与OPG呈显著正相关(r=0.929,P0.01),而与TNF-α(r=-0.936,P0.01)及RANKL(r=-0.951,P0.01)呈显著负相关。结论老年类风湿关节炎患者外周血低表达OPG而高表达促炎因子,这与其骨密度值降低密切相关,OPG有望成为改善此类患者骨质代谢的新靶点。     

低体重与护骨素基因启动子T149-C和A163-G多态性与骨质疏松的关系

目的 探讨护骨素(OPG)基因启动子区T149-C和A163-G多态性及低体重联合作用对绝经后健康女性和绝经后骨质疏患者骨密度(BMD)的影响.方法 以134例广州地区居住10年以上无亲缘关系的绝经汉族女性为研究对象.骨质疏松症73例,绝经后健康女性61例作对照组.随机抽取25个样本经SSCP-PCR法寻找异常迁移条带,再采用测序方法确定扩增区域中的单核苷酸突变位点,最后采用PCR限制性片段长度法(RFLP)对所有样本进行分析;双能X线吸收法测定BMD.结果 在73例绝经后骨质疏松症女性和61例绝经后健康女性OPG启动子扩增区中,找到两个单核苷酸点突变多态性位点,T149-C和A163-G.分析显示这两个多态性位点基因型频率在两组中的分布均符合Hardy-Weinberg定律.T149-C和A163-G多态性单一基因型和复合基因型的频率分布在两组实验对象间差异无统计学意义(P＞0.05).对单一基因型及其复合基因型的BMD分析显示绝经后骨质疏松症女性的腰椎和髋部BMD明显低于绝经后健康女性.绝经后骨质疏松症患者的体质指数(BMI)也明显低于绝经后健康女性[分别为(22.5±3.0)kg/m2和(24.4±3.6)kg/m2,P＜0.01].结论 T149-C和A163-G多态性对绝经后骨质疏松患者和绝经后健康女性的骨量影响没有协同作用;单一的和复合的T149-C和A163-G多态性各基因型不能作为预测中国汉族女性发生骨质疏松的遗传标志,但可能是骨质疏松发生的易感基因.     

基因多态性与骨密度的相关性

骨密度受遗传因素影响,骨密度测定是诊断骨质疏松的主要依据.维生素D受体、Ⅰ型胶原、雌激素受体、降钙素受体参与骨形成和骨代谢,其基因多态性决定骨密度.研究发现Wnt蛋白、人类白细胞抗原等基因多态性也与骨密度有关.本文就基因多态性与骨密度的相关性进行论述.     

Soluble receptor activator of NFkappa B-ligand and osteoprotegerin in rheumatoid arthritis - relationship with bone mineral density,disease activity and bone turnover

The aim of our study was to investigate determinants of bone mineral density (BMD) measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN) in patients with rheumatoid arthritis (RA) with special respect to bone resorbing proinflammatory cytokines and their physiological antagonists. In 142 RA patients the following parameters were measured in parallel with BMD: serum levels of soluble receptor activator of nuclear factor kappa-B-ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-6, soluble glycoprotein 130 (sgp130), 25-hydroxyvitamin D3 (25OHD₃), 1,25-dihydroxyvitamin D3 (1,25[OH]₂D₃), intact parathyroid hormone, osteocalcin, ionized calcium, renal excretion of pyridinolin and deoxypyridinolin, C-reactive protein, and erythrocyte sedimentation rate (ESR). No significant differences of sRANKL, OPG, IL-6, and spg130 were found between patients with osteoporosis (47.9% of patients), osteopenia (36.6%), and normal BMD (15.5%). However, total sRANKL was significantly higher in postmenopausal women with osteoporosis at FN than in those without (p < 0.05) and showed a negative correlation with BMD-LS in patients older than 60 years (p = 0.01). BMD-LS and BMD-FN (p < 0.001) and total sRANKL (p < 0.01) were negatively related with the age of the patients. Only IL-6 (positive correlation, p < 0.001) and 1,25(OH)₂D₃ (negative correlation, p < 0.001) but not sRANKL, OPG, and sgp130 were related to disease activity. Using multiple linear regression analysis, menopause was identified as the crucial negative determinant of BMD-LS (R ² = 0.94, p = 0.001), whereas cumulative glucocorticoid dose (β = −0.80, p = 0.001) and ESR (β = −0.44, p = 0.016) were the negative determinants of BMD-FN (R ² = 0.86, p = 0.001). The results indicate that influences of age and gender must be considered in investigations on the relationship between BMD and sRANKL in RA and that high serum levels of sRANKL seems to be associated with osteoporosis only in subgroups of RA patients.     

C950T and C1181G osteoprotegerin gene polymorphisms in myeloma bone disease

Objectives

Bone disease is one of the hallmarks of multiple myeloma (MM). The role of osteoprotegerin (OPG) in the RANK/RANKL/OPG signaling system is well defined in the myeloma bone disease. Polymorphisms of the TNFRSF11B gene encoding OPG have been studied in various bone diseases. However, relationship between the levels of OPG and development of bone lesions regardless of RANKL is yet unknown. In this study, the effects of OPG gene polymorphism on the development of bone lesions in MM were investigated.

Methods

C950T and C1181G polymorphisms of the OPG gene were studied in 52 MM patients (36 with bone lesions and 16 without bone lesions) and in another 20 control subjects using DNA sequencing.

Results

1181 G and 950 T alleles were overrepresented in MM patients having bone lesions. 950 TT/1181 GG haplotype frequency and TT/GG combined haplotype were also higher in MM patients having bone lesions compared to MM patients without bone lesions or to control.

Discussion

This is the first study searching for the relationship between OPG gene variants C950T (promoter), C1181G (exon 1), and myeloma bone disease. It was concluded that the presence of polymorphic 1181 G/950 T alleles and 950 TT/1181 GG genotypes may play a role in the development of bone disease.     

Association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene and bone mineral density: a meta-analysis

The association between the A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density (BMD) has been studied, but results have been mixed. Accordingly, the authors performed a meta-analysis on studies on the association between the A1330V LRP5 polymorphism and BMD. Appropriate studies were identified using MEDLINE and by manual searching. A total of 7 separate comparisons were considered in this meta-analysis. Individuals with the AA genotype showed significantly higher lumbar BMD than those with the AV/VV or VV genotype. Weighted mean differences (WMDs) were 0.147 g/cm² (95% confidence interval [CI] 0.069–0.224, P < 0.001) and 0.182 g/cm² (95% CI 0.024–0.340, P = 0.024) without between-study heterogeneity for AA versus AV/VV and AA versus VV, respectively. Six studies analyzed femur neck (FN) BMD. Individuals with the AA genotype had a significantly higher FN BMD than those with the AV/VV genotype (WMD = 0.165 g/cm², 95% CI = 0.087–0.215, P < 0.001), without between-study heterogeneity. Trochanter BMD was measured in three studies. Results showed that subjects with the AA genotype tended to have higher BMD than patients with the AV or VV genotype (WMD = 0.136 g/cm², 95% CI = −0.002 to 0.274, P = 0.053). In conclusion, this meta-analysis shows that the LRP5 A1330V polymorphism is associated with BMD, and that individuals with the AA genotype have a higher BMD than those with the AV/VV or VV genotype.     

维生素D受体基因型与骨密度的关系

目的　了解维生素D受体 (VDR)基因的BsmI多态性在中国人群中的分布 ,并进一步探讨其与骨密度 (BMD)的关系。方法　应用聚合酶链反应 -限制性片断长度多态性解析 (PCR RFLPs)技术检测了 1 86例在长春地区生活 1 0年以上的无亲缘关系的绝经前健康汉族女性VDR基因型 ,用双能X线骨密度仪 (DEXA)测腰椎BMD ,同时考察它们之间的关系。结果　VDR基因型分布频率为Bb:2 3例 (1 2 .4% ) ,bb :1 63例(87.6 % ) ,BB型缺如。b等位基因在本组人群中分布高达 93 .8%。各型的BMD值分别为 :Bb型 (1 .1 87± 0 .0 88) g/cm2 ,bb型 (1 .1 53± 0 .1 1 2 ) g/cm2 ,两组比较差异无统计学意义 (P >0 .0 5)。结论　中国长春地区绝经前汉族女性的VDR基因的BsmI多态性与骨密度间无相关关系。     

甲状旁腺素基因多态性对正常女性骨密度的影响

目的 探讨正常女性人群甲状旁腺素（PTH）基因多态性对多部位骨密度的影响。方法 对596名平均年龄（46．3±13．7）岁女性志愿者基因组DNA作限制性内切酶BstBⅠ的PCR-RFLP检测以确定其基因型，存在Bst BⅠ限制性酶切位点用“B”表示，不存在则用“b”表示；采用Hologic QDR4500A DEXA骨密度仪测定不同骨骼部位的骨密度，即腰椎（L1～L4）正位总体（AP）和仰卧侧位总体（Lat）、股骨颈（FN）、髋部总体（T—hip）、Ward三角（Ward）、大转子（Troch）和前臂超远端（RUUD）及远端总体（RUT）的骨密度。结果 （1）596名健康女性PTH基因多态性符合Hardy—Weinberg平衡，BB、Bb和bb基因型分布频率分别为0．784、0．208和0．008；B、b等位基因频率为0．888和0．112。347名绝经后妇女PTH基因多态性频率调查结果显示BB、Bb和bb基因型分布频率分别为0．781，0．210和0．009，B、b等位基因频率为0．886和0．114；绝经前妇女PTH基因多态性频率与绝经后妇女差异无统计学意义。（2）方差分析显示女性BB和Bb基因型在AP、Lat、FN、T-hip、Ward、Troch、RUUD和RUT的骨密度差异无统计学意义。（3）Logistic分析结果显示PTH基因型不是骨量减少或骨质疏松的独立相关变量。结论 女性PTH基因多态性对骨密度的变异无明显影响。