COL4A1基因多态性与中国女性骨密度关系分析

目的研究COL4A1基因多态性与中国农村女性骨密度关系。方法采用双能X线吸收仪对343名女性研究对象进行腰椎及股骨扫描,应用PCR-限制性片段长度多态性(PCR-RFLP)方法检测COL4A1基因(谷酰氨酸Q1334H组氨酸)多态位点基因型,用广义线性模型分析此位点多态性与腰椎2~4及股骨骨密度关系。结果在调整环境危险因素后,均未显示COL4A1基因H1334H基因型与股骨颈、腰椎2~4骨密度相关(P=0.409、0.705)。结论在中国农村女性人群中COL4A1基因Q1334H多态性与股骨颈、腰椎2~4骨密度无显著相关性。     

COL4A1基因SNPrs3783107多态性与女性骨密度的关系

目的 研究COL4A1基因多态性与包头市区女性骨密度的关系。方法 采用病例-对照研究方法,收集在包头医学院第一附属医院进行健康体检的596例女性流行病学资料,用双能X线吸收仪对研究对象进行骨扫描。应用PCR-RFLP方法检测COL4A1基因型。用广义线性模型分析此位点多态性与腰椎及股骨颈骨密度关系。结果 在调整环境混杂因素前后,均显示COL4A1基因SNPrs3783107突变基因型与绝经前女性股骨颈和腰椎骨密度降低呈显著相关(P =0. 011、0. 004),但与绝经后的骨密度无显著相关性(P =0. 090、0. 093)。结论 COL4A1基因SNPrs3783107多态性与包头市区绝经前女性股骨颈及腰椎骨密度显著相关。     

常染色体隐性遗传Alport 综合征一家系COL4A3及COL4A4基因突变分析

目的 通过对有近亲婚配史的Alport综合征一家系Ⅳ型胶原α3和α4链的 COL4A3/COL4A4 基因分析，明确常染色体隐性遗传Alport综合征的基因突变,为该病的基因诊断和家系遗传咨询提供更为全面的理论基础｡ 方法 PCR扩增先证者DNA COL4A3/COL4A4 基因的共98个外显子，经直接测序，寻找突变位点，对有意义的突变经限制性内切酶AvaⅡ酶切在家系中分析验证｡ 结果 在该患者中共发现1个错义突变和10个序列变异｡其中在COL4A3 基因上发现一个位于42号外显子上的错义突变 G3725A,导致蛋白质Gly1242Asp的突变｡错义突变在患者中是纯合子，携带者中是杂合子，其他正常家系成员及筛查100条正常人染色体，未发现该突变｡10个序列变异为单核苷酸多态性改变｡ 结论 报道了一个国内较少见的常染色体隐性遗传Alport 综合征家系，同时经基因突变筛查发现Ⅳ型胶原α3链的一个新的致病性的基因突变｡     

长春市汉族人群COL1A1启动子区多态性与骨质疏松症的相关性

目的研究长春市汉族人群Ⅰ型胶原α1链基因(COL1A1)启动子区-1997G/T、+1245G/T多态性及其与骨质疏松的关系。方法 (1)抽取受试人群外周静脉血5 ml,提取血清DNA。(2)应用实时荧光定量PCR仪扩增目的基因的DNA片段。(3)采用TaqMan探针法对-1997G/T及+1245G/T位点进行等位基因鉴别。(4)应用双能X线骨密度仪测定骨密度(BMD),将374例受试人群分为骨密度正常、骨质疏松、骨质疏松性骨折3组。结果长春市汉族正常人群COL1A1-1997G/T转换中,GG基因型占38.40%,GT基因型占46.38%,TT基因型占15.22%,以GT基因型为主;骨质疏松患者女性GG等位基因型所占比例大于男性,GG基因型占44.39%,GT基因型占43.37%,TT基因型占12.24%;骨质疏松骨折患者GG基因型为主,占47.50%,GT基因型占35.00%,TT基因型占17.50%。骨质疏松组女性GG基因型BMD低于GT、TT基因型,但差异无统计学意义(P均0.05);骨质疏松骨折组女性GG基因型BMD显著低于GT、TT基因型(P均0.05)。COL1A1+1245位点G/T转换,在正常人群中发现GT杂合型2例,占总数的0.53%,其余均为GG基因型。结论 COL1A1-1997G/T转换中正常人群以GT基因型为主,骨质疏松患者和骨质疏松骨折患者以GG基因型为主。骨质疏松患者和骨质疏松性骨折患者女性GG基因型BMD均低于GT、TT基因型。COL1A1-1997G/T与BMD显著相关,+1245G/T与BMD无相关性。     

性连锁Alport综合征COL4A5基因突变检测

目的 检测16个家系20例性连锁Alport综合征患者COL4A4基因突变。方法：采用PCR－变性凝胶梯度电泳（DGGE）－直接测序法检测患者COL4A5基因中30个外显子及其相邻内含子区域（外显子1－25，31，32，41，50，51），另选取100例政党人外周血DNA作为对照。结果 共发现4种突变，包括1种位于1号外显子的无义突变（266C→T谷氨酰胺22终止密码），1种位于31号外显子上的错义突变（2575G→T甘氨酸852缬氨酸），以及2种分别位于1，25号内含子区域的剪接突变（283＋1G→T，2150＋1G→T）。结论 COL4A5基因为性连锁Alport综合征的致病基因，突变类型多样，尚未发现热点突变。类似于外显子突变，内含子突变同样具有致病意义。患者临床症状典型，查阅基因库，此4种突变均为首次报道。     

基于数据库挖掘分析COL4A1基因在结直肠癌中的表达及意义

目的利用公开的生物信息学数据库分析COL4A1基因在结直肠癌中的表达以及意义。方法应用Oncomine数据库探讨COL4A1基因在结直肠癌组织中的表达;应用GEPIA数据库分析COL4A1基因的表达水平,在结直肠癌患者中的病理分期以及生存期的相关性分析;应用MethHC甲基化数据库分析COL4A1基因启动子区的甲基化水平,分析COL4A1的表达与甲基化的关系;应用String数据库分析与COL4A1蛋白相互作用的蛋白网络及可能参与的机制。结果在结直肠癌肿瘤组织中,COL4A1基因的mRNA表达水平显著地高于正常结直肠组织,COL4A1基因的mRNA表达水平与结直肠癌患者的临床病理分级及患者总体生存持续时间水平无显著的相关性。结直肠癌中COL4A1基因DNA启动子区的甲基化表达水平较正常的结直肠黏膜组织显著升高,且COL4A1基因表达与结肠癌组织中COL4A1启动子区甲基化表达水平呈正相关。COL4A1基因可能ECM受体相互作用、局部受体粘附等信号传递通路中发挥作用。结论结直肠癌组织中COL4A1基因高表达,其在结直肠癌中的作用及机制需进一步研究阐明。     

导致家族性血尿的 COL4A4基因遗传变异分析

目的:通过对1个家族性血尿家系进行遗传变异筛查,为家族性血尿病变提供遗传线索和证据。方法:本研究纳入的研究对象为1个4代含20名成员的家族性血尿家系。对该家系进行临床资料和实验室检查结果的收集和整理,留取家系中11名成员的外周血并用盐析法提取DNA用于遗传分析。首先选取包括先证者在内的3名家系成员进行全外显子组测序,根...     

COL9A2链19外显子单核苷酸基因多态性与腰椎间盘退变相关性分析

目的:探讨Ⅸ型胶原蛋白 A2(COL9A2)链第19号外显子单核苷酸多态性与腰椎间盘退变的关系 方法:采用病例-对照研究方法,101例中国北方汉族腰椎间盘退变(LDD)与98例中国北方汉族非LDD患者,提取全血基因组DNA,对COL9A2链第19外显子进行扩增并测序,观察其单核苷酸多态性与LDD的相关性结果:在测序结果中发现,COL9A2链第19外显子中存在Gln326Trp和Gln326Arg多态性,并且在退变组与作退变组中分别为61、5和52、11.Gln326Trp和Gln326Arg多态性在退变组与非退变组相比无统计学差异(P＞o.05).对退变组分析,COL9A2链第19外显子Gln326Trp和Gln326Arg多念性与腰椎间盘退变程度、退变节段位置及退变节段数量无明显相关性(P＞0.05).结论:在中国北方汉族中,COL9A2第19外显子单核苷酸多态性可能不是决定腰椎间盘退变的主要危险因素.     

褪黑素受体1B基因多态性与青少年骨密度的相关性

目的探讨褪黑素受体1B基因(MTNR1B)多态性与骨密度之间的相关性。方法选取140名16~20岁之间的正常女性,采用双能X线骨密度吸收仪测量双侧近端股骨的骨密度。同时,采取外周静脉血,采用试剂盒提取DNA。根据人类单倍体图计划(HapMap)提供的汉族人数据,我们在MTNR1B基因上选取了6个标签SNP(tagSNPs)。通过PCR-RFLP的方法检测褪黑素受体1B基因上6个标签SNP的基因型。采用ANOVA的统计学方法比较不同基因型对应骨密度大小。结果MTNR1B基因6个多态性位点各基因型所对应的骨密度,没有明显差异(P>0.05)。结论褪黑素受体1B基因多态性与骨密度之间没有相关性。     

Gene polymorphisms,bone mineral density and bone mineral content in young children:the Iowa bone development study

We examined the association of candidate gene polymorphisms with bone mineral density (BMD) and bone mineral content (BMC) in a cohort of 428 healthy non-Hispanic white children participating in the Iowa Bone Development Study, a longitudinal study of determinants of bone accrual in childhood. BMD and BMC measurements of the hip, spine and whole body were made using a Hologic 2000 Plus densitometer in 228 girls and 200 boys ages 4.5–6.5 years. Genotypes at 14 loci representing eight candidate genes [type I collagen genes (COL1A1 and COL1A2), osteocalcin, osteonectin, osteopontin, vitamin D receptor (VDR), estrogen receptor (ER), androgen receptor (AR)] were determined. Gender-specific and gender-combined prediction models for bone measures that included age, weight, height (and gender) were developed using multiple linear regression analysis. COL1A2 and osteocalcin genotypes were identified as having the strongest and most consistent association with BMD/BMC measures. Osteonectin, osteopontin and VDR translation initiation site polymorphisms were associated with some individual bone measures, but none of the associations was as consistent as those identified for the COL1A2 and osteocalcin genes. No association was identified with COL1A1 (RsaI and Sp1), VDR (BsmI) and ER polymorphisms (PvuII, XbaI, TA) and BMD/BMC. However, we identified significant gene-by-gene interaction effects involving the ER and both VDR and osteocalcin, which were associated with BMD/BMC. Our data suggest that genetic variation at multiple genetic loci is important in bone accrual in children. Moreover, the combination of genotypes as several loci may be as important as a single genotype for determining BMD and BMC.     

Lack of association between calcium-sensing receptor gene "A986S" polymorphism and bone mineral density in Hungarian postmenopausal women

Calcium-sensing receptor (CaSR) is an attractive candidate gene for osteoporosis susceptibility. The CaSR “A986S” genotype has been shown to have an effect on serum calcium. Recently, an association has been reported between the CaSR gene A986S polymorphism and bone mineral density in healthy white girls. In this study, we examined whether CaSR gene A986S polymorphism is associated with decreased bone mass in 230 Hungarian postmenopausal women. From this cohort, 108 osteoporotic patients were compared with 122 healthy control women. Bone mineral density (BMD) was measured at the lumbar spine (L2–4) and femoral neck using dual-energy X-ray absorptiometry. Allele-specific polymerase chain reaction was used to amplify A986S polymorphisms of the CaSR gene. We found no difference in the distribution of different alleles or genotypes between groups (p = 0.762). No significant effect of CaSR genotype on BMD was observed either in the whole population or in the subgroups. Our data do not support the idea that CaSR gene A986S polymorphism has an impact on bone mass.     

Apparent bone mineral density estimated from DXA in healthy men and women

The aim of this study was to measure bone mineral density (BMD) in healthy people and examine the influence of age, anthropometry, and postmenopause on calculated bone mineral apparent density (BMAD). The study included 541 healthy subjects (249 men and 292 women), aged 20 to 79 years. Anthropometric measurements included height, weight, and body mass index (BMI). Bone mineral content (BMC) and areal BMD were measured at the lumbar spine and proximal femur, using dual-energy X-ray absorptiometry (DXA). The calculation of volumetric density relied on the formula BMAD=BMD/BA (where BA = bone area). Association between densitometric parameters and age, height, weight, and postmenopause was analyzed with multiple regression. BMC and BMD decreased with age, especially in postmenopausal women. The average annual bone loss in spine was 0.2% in both sexes, whereas femur loss was 0.5% in men and 0.3% in women. Bone area slightly increased with age in both sexes, and BMD loss after the age of 50 could be attributed to bone area increase. To minimize the effect of bone size on bone density, volumetric density and areal density were regressed to age, anthropometry, and postmenopause. Age and postmenopause were significantly associated with BMD and BMAD in the spine and femur. Furthermore, BMD showed a stronger association with height and weight than BMAD, in both regions. Weaker association of body height and weight with BMAD than with BMD suggests that BMD depends on the bone size and body size and that the different BMDs could be the consequence of the difference in those parameters.     

牙齿缺失与骨密度关系的研究

目的系统骨丢失与牙槽骨局部骨丢失致牙齿缺失之间的关系尚不清楚，通过检测健康藏族妇女的骨密度及其牙齿缺失状态，探讨其相关性。方法随机选择西藏拉萨40—79岁健康藏族妇女(无牙周疾病治疗史)135人，检查牙齿缺失状况确定缺牙原因。问卷调查排除系统病和服用影响骨密度和钙磷代谢药物史。同时用MetriScan TM(美国Alara公司提供)指骨骨密度仪进行骨密度测量，应用SPSS软件统计分析。结果随年龄增长，因牙周病而缺牙的人占同年龄人数的百分率逐渐升高，骨密度逐渐降低。结论骨质疏松症是牙周病的危险因子之一。     

Association of estrogen receptor α gene polymorphisms with bone mineral density in Chinese women: a meta-analysis

Introduction and hypothesis A large number studies have examined the association between estrogen receptor alpha (ESR-α) gene polymorphisms and bone mineral density (BMD) in the Chinese population. We conducted a meta-analysis to assess their pooled effects. Methods We searched for all published articles indexed in MEDLINE, the Chinese Biomedical Database, and the Chinese Journal Full-text Database from January 1994 to April 2006. Any cross-sectional study that tested the association between ESR-α PvuII or XbaI genotypes and BMD at the femoral neck or spine in Chinese women was included in the review. Data were extracted independently by two reviewers using a standardized data extraction form. Sixteen eligible studies involving 4,297 Chinese women were identified. Results The overall frequencies of X and P alleles were 28% and 40%, respectively. The PvuII polymorphism was statistically significantly associated with BMD at the femoral neck (P = 0.038 for PP = Pp = pp) but not at the lumbar spine in all women. The BMD difference for the contrasts of PP versus Pp/pp genotypes was −0.0105 (95%CI, −0.0202 ∼ −0.0008) g/cm² (P = 0.036). The XbaI polymorphism was not associated with BMD at the femoral neck or lumbar spine. Conclusion The PvuII polymorphism had a very weak association with femoral neck BMD whereas XbaI polymorphism was unlikely to be a predictor of femoral neck or spine BMD in Chinese women.     

骨胶原与骨质疏松骨密度及骨生物力学的相关性研究

目的探讨骨胶原含量在绝经后骨质疏松症的发生、发展及在骨质疏松性骨折中的作用。方法取7个月龄未交配雌性SD大鼠60只，随机分为四组，A组：对照组（sham组）；B组：切除卵巢组；C组：切除卵巢＋雌激素治疗组；D组：切除卵巢＋降钙素治疗组。除A组外，其他三组通过切除双侧卵巢法12周后制成骨质疏松模型，24周后分别行k的力学特性、右侧股骨三点弯曲试验、羟脯氨酸含量、k骨密度（BMD）测定，Masson三色染色法显示骨胶原形态。结果A、C、D组与B组在k羟脯氨酸含量、BMD、k压缩力学参数值、右侧股骨生物力学参数值、骨胶原染色含量及形态方面差异均有统计学意义（P〈0．05），而A、C、D组之间差异无统计学意义（P〉0．05）。统计学分析显示羟脯氨酸含量与BMD及骨生物力学参数值呈直线相关性。结论骨质疏松的发生与骨胶原含量下降有关。骨胶原含量的下降与BMD降低及骨生物力学改变呈相关性。应用雌激素和降钙素治疗去势后骨质疏松大鼠，不仅可以提高其BMD含量和骨生物力学性能，而且还可以提高骨胶原的含量。     

糖皮质激素受体基因多态性与骨密度关系的研究

目的 以体内糖皮质激素水平正常的人群为研究对象,研究糖皮质激素受体(GR)基因多态性与骨密度间的关系。方法 用特异的等位基因PCR方法检测人群的GR基因型,用DEXA检测腰椎、股骨各处骨密度。结果 在男性病例,各基因型间BMD的T值无明显统计学差异;在女性病例,各基因型间BMD的T值比例:TT型比CC型T值明显升高(P<0.05)。结论 GR基因外显子8的678位点突变(C→T),可使女性腰椎骨密度增加,具有骨密度保护作用。     

Relationship between grip strength and bone mineral density in healthy Hong Kong adolescents

Summary  This study evaluated the magnitude of the correlations among grip strength, bone mineral density (BMD) and bone mineral content (BMC), after controlling for weight, height, pubertal development, weight-bearing activities and calcium intake. The results lead to the conclusion that grip strength is an independent predictor of bone mass in both sexes. The relationship between muscle strength and bone mass is systemic. Introduction  Previous studies had shown a site-specific relationship between muscle strength and bone in pubertal children. This study evaluated the magnitude of the correlations among grip strength, bone mineral density (BMD) and bone mineral content (BMC) at distant bone. Methods  Cross-sectional data of 169 11- to 12-year-old boys and 173 10- to 11-year-old girls came from the baseline result of a cohort study. Grip strength, BMD, BMC, weight, height, pubertal development, weight-bearing activities and calcium intake were measured. Pearson correlations and multiple regressions were used to calculate univariate and adjusted associations among grip strength and bone mass at distant bone. Results  Significant correlations were shown between grip strength and bone mass at hip, spine and whole body (boys: BMC:0.72–0.74, BMD:0.38–0.60; girls: BMC:0.71–0.72, BMD:0.44–0.63; p<0.0001). Multiple regressions with all covariates showed that about 70% and 50%, respectively, of the variations in BMC and BMD could be explained but not for whole body BMD. Grip strength was an independent predictor of bone mass, except hip BMD in boys and whole body BMD in girls. Stepwise regression showed that grip strength was a robust predictor in both sexes. Prediction models by grip strength and weight explained about 60% and 40% of the variations in BMC of different sites and in BMD of hip and spine, respectively. Conclusions  We found that grip strength is an independent predictor of bone mass in both sexes. The relationship between muscle strength and bone mass is systemic.     

牙周附着丧失与骨密度关系的研究

目的探讨健康藏族成年妇女骨密度状态与牙周附着丧失的关系。方法随机选择35～69岁健康藏族成年妇女（无牙周疾病治疗史）141人，检查牙周组织状态，确定牙周附着丧失牙数及缺失牙数。问卷调查排除全身疾病和服用影响骨代谢药物史。并用MetriScan TM（美国Alara公司提供）指骨骨密度仪进行骨密度测量，采用单因素方差分析方法进行统计学分析。结果每一年龄段内，牙周附着丧失不同状态下妇女的骨密度在统计学上没有显著差异，但随着年龄增高，牙周附着丧失及缺失牙严重程度增加。结论骨密度减低是牙周附着丧失的危险因子。