VDR基因SNPs多态性与新疆维、汉民族育龄女性腰 椎峰值骨密度的关系

目的探讨新疆地区维吾尔族、汉族两民族育龄女性维生素D受体(VDR)基因多态性与腰椎峰值骨密度的关系。方法分别对新疆地区无亲缘关系、年龄20~40岁的305例汉族健康妇女和216例维吾尔族健康妇女进行CDX2(rs11568820),TaqI(rs731236),Tru9 I(rs757343)位点多态性检测,用定量CT(QCT)骨密度仪测定腰椎骨密度(BMD)。结果维、汉族育龄女性腰椎骨峰值出现的年龄段略有不同,但都在35岁达到。两民族女性CDX2(rs11568820),TaqI(rs731236),Tru9 I(rs757343)位点基因型及等位基因频率分布均符合Hardy-Weinberg平衡定律;CDX2(rs11568820)基因型频率在维、汉两民族妇女中比较,差异有显著性(P0.05)。TaqI位点T和t等位基因分布频率在维族和汉族育龄女性中差异有有统计学意义(P0.05)。各基因型与BMD的关系显示:CDX2(rs11568820),TaqI(rs731236),Tru9 I(rs757343)位点多态性与维族、汉族腰椎峰值骨密度均无明显相关(P0.05)。但VDR基因TaqI携带Tt基因型的骨密度值在汉族与维族妇女比较时存在显著性差异,同样携带Tt基因型的维族女性骨密度比汉族女性高。Tru9I在汉族女性组中携带Tt基因型,其骨密度比携带tt型和TT型高,结论 VDR SNPs的基因型与腰椎峰值骨密度具有种族差异性,CDX2(rs11568820),TaqI(rs731236),Tru9 I(rs757343)位点多态性对新疆地区维、汉族育龄女性腰椎峰值骨量无明显影响。     

东亚人群LRPS基因A1330V位点多态性与骨密度相关性的M eta分析

目的 利用Meta分析的方法,综合评价LRPS基因A1330V位点多态性与东亚人群骨密度(BMD )的相关性。方法 计算机检索Pubmed , Embase、中国生物医学文献数据库和万方数据库数据库等,并手工检索相关杂志,收集有关东亚人群LRPS基因A1330V位点多态性的基因型频率与BMD相关性的研究。检索时间截止至2012年11月。在评价纳人研究质量,提取有效数据后,采用Stata 12.0软件进行Meta分析。结果 共11项研究符合既定的纳人和排除标准,合计5906名研究对象。Meta分析结果显示:AA基因型较AV/VV基因型腰椎BMD高,且差异有统计学意义[SMD =0.107, 95% CI (0.044,0. 171)。在股骨颈BMD方面,AA基因型高于AV/VV基因型[ SMD =0. 190, 95% CI (0. 034, 0. 346) ]。 AA基因型的挠骨、全身BMD也高于AV/VV基因型。但是,AA基因型群体的转子间BMD与AV/VV基因型的差异无统计学意义[SMD =0. 090, 95% CI(-0.029, 1. 143)]。除腰椎、转子间BMD以外,AA基因型群体的股骨颈、挠骨以及全身BMD高于VV基因型,但此基因型间比较的纳人研究数量过少,证据尚不充分。结论 本Meta分析结果提示,东亚人群中LRPS基因A1330V位点的突变可能与骨密度的变化具有相关性,尤其AA基因型人群在股骨颈、腰椎部位有比AV/VV或VV基因型人群更高的骨密度值。但目前的结论尚需进一步大样本、高质量的研究去验证。     

老年髋部骨折与降钙素受体基因多态性的关系

目的研究降钙素受体(CTR)基因多态性与老年髋部骨折患者骨密度(BMD)的关系,探讨原发性骨质疏松症(OP)发病的分子机制。方法选取老年髋部骨折患者105人为病例组,并以年龄、性别作配比因素,选取107例非骨折人群为对照组。采用聚合酶链反应-限制性长度多态性(PCR-RFLP)技术对受试者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 212例受试对象中,CTR基因型分别为CC型187例(88.21%),CT型25例(11.79%)。病例组和对照组及不同性别间基因型无显著差异。212例受试者各部位的骨密度与年龄呈负相关,与体质量指数正相关。分析基因型与骨密度的关系显示,CT型除在腰椎侧位(L2～L4)及Ward'三角的骨密度比CC型的骨密度值有显著性升高外,其他部位骨密度值之间的差异无统计学意义。结论 CTR基因多态性尚不能作为老年髋部骨折危险性的遗传标志。     

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。     

ERα基因SNPs与乳腺癌芳香化酶抑制剂治疗所致骨代谢异常的关系

目的探讨接受芳香化酶抑制剂(AIs)治疗的乳腺癌患者ERα基因rs9340799、rs2234693位点单核苷酸多态性(SNPs)与AIs所致骨代谢异常的相关性。方法随机选取160名接受AIs治疗的乳腺癌术后患者,排除影响骨代谢的疾病,提取全基因组DNA并进行PCR扩增,对rs9340799、rs2234693位点进行单向测序;用双能X线吸收法测定腰椎(L1-4)骨密度(BMD)。结果 ERα基因rs9340799位点各基因型受试者的腰椎BMD存在显著性差异(P0.01),A/A型高于A/G型及G/G型(P0.01);rs2234693位点各基因型间的腰椎BMD亦存在显著性差异(P0.01),T/T型、C/T型均高于C/C型(P0.01)。去除绝经年数的影响,两位点各基因型受试者间腰椎BMD的差异仍具有统计学意义(P0.01)。根据接受AIs治疗时间分层分析,两位点SNPs与服药1年内受试者的腰椎BMD相关(P0.01),在服药1年及以上的受试者中,rs9340799位点SNP与腰椎BMD相关(P0.05)。结论 ERα基因rs9340799、rs2234693位点SNPs与接受AIs治疗的乳腺癌患者的腰椎BMD存在显著性关联。与纯合基因型A/A型、T/T型相比,杂合基因型A/G型、C/T型及纯合基因型G/G型、C/C型更具有发生骨代谢异常的可能。     

雌激素受体α基因多态性与新疆维、汉两民族妇女腰椎峰值骨密度的关系

目的探讨新疆地区维吾尔族(维族)、汉族两民族妇女雌激素受体(ER-α)基因多态性与腰椎峰值骨密度的关系。方法分别对乌鲁木齐地区无亲缘关系、年龄20～40岁的160例汉族健康妇女和135例维吾尔族健康妇女进行PCR-RFLP测定雌激素受体α基因XbaI及PvuⅡ多态性,用定量CT(QCT)骨密度仪测定腰椎骨密度(BMD)。结果维、汉族女性骨密度均值比较,差异有显著性(P<0.05)。维、汉族妇女ER-α的基因型及等位基因频率分布均符合Hardy-Weinberg平衡定律;XbaI及PvuⅡ多态性基因型频率及等位基因频率在维、汉两民族妇女中比较,差异均有显著性(P<0.05)。协方差方法分析各基因型与BMD的关系显示:仅PvuⅡ多态性与维族妇女L2-4BMD值显著相关(P<0.05),Pp/pp基因型在L2-4BMD值明显低于PP基因型,差异有显著性(P<0.05)。结论 ER-α基因XbaI多态性对新疆地区维、汉族妇女腰椎峰值骨量无潜在影响;PvuⅡ多态性对维族妇女腰椎峰值骨量的达到和维持有关,与汉族无关。     

骨质疏松症与降钙素受体ALU I C1377T多态性的相关性

目的 探讨降钙素受体基因C1377T单核苷酸多态性在山东半岛汉族人群中的分布规律及与原发性骨质疏松的关系.方法 应用聚合酶链反应一限制性片段长度多态性方法 ,测定290名山东半岛汉族成年人和77名骨质疏松性骨折患者降钙素受体基因型并计算出基因型及等位基因频率;用双能X线吸收法测定腰椎和股骨近端的骨密度.比较不同基因型与各部位骨密度是否存在相关.结果 本研究人群降钙素受体基因型频率分布均符合Hardy-Weinberg定律(χ~2=1.325,P＞0.05).367名受试人群基因型频率分布依次为CC型占88.6%,CT型占11.4%,TT型占0%.在将年龄和体质量指数进行校正后发现CC基因型较CT基因型在腰椎(P＜0.05)、wards三角(P＜0.05)有较高的骨密度.骨量正常组各基因型与骨质疏松性骨折组之间差异无统计学意义(χ~2=1.547,P＞0.05).结论 CC型是山东半岛汉族人群最常见的类型,降钙素受体基因型与腰椎、wards三角部位BMD有关联,CT型具有较低骨密度,提示CTR基因型C1377T多态性可能成为胶东半岛汉族人群发生骨质疏松危险性的遗传标志.     

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。     

两个新钙感觉受体基因多态性与中国女性骨密度相关性研究

目的钙感觉受体(CaSR)基因是引人关注的与骨质疏松症敏感性相关的侯选基因,为了解CaSR基因两个新多态位点与中国女性人群骨密度(BMD)的关系。方法采用双能X线吸收仪对352名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(PCRRFLP)方法检测CaSR基因R990G和E1011Q两个新多态位点基因型,用广义线性模型分析CaSR基因与腰椎及股骨BMD关系。结果发现CaSR基因的E1011Q多态位点在调整相关影响因素前后均与女性股骨颈、股骨柄和股骨三角区的BMD呈显著相关,P值分别为0.011、0.04和<0.001;R990G多态位点在调整影响因素前后,显示与女性股骨颈密度有相关趋势P=0.055,而A986S基因多态未显示与股骨、腰椎BMD相关。结论这一结果提示,CaSR基因E1011Q多态性可能是中国女性股骨BMD降低的危险因素。这个发现的意义及是否适用于大样本人群还有待进一步研究证实。     

内蒙古地区蒙古族男性雌激素受体基因多态性与骨密度关系的研究

目的 探讨内蒙古地区蒙古族男性雌激素受体a(estrogen receptor,ER)基因多态性与骨密度(BMD)的关系.方法采用PCR- 限制性片段长度多态性检测500名无血缘关系的蒙古族健康男性ER- a基因XbaⅠ和PvuⅡ多态性,结合双能X 线吸收仪检查腰椎(L2-L4)和股骨近端股骨颈( femoral neck)、大转子区( trochanter) 和Ward三角部位BMD.结果 本研究人群XbaⅠ和PvuⅡ等位基因频率分布符合Hardy-Weinberg 定律.PvuⅡ多态性与腰椎(L2-L4)和Ward三角部位BMD 值均有相关性( P<0.05),而XbaⅠ多态性与各部位BMD 值均无相关性; PP基因型在上述部位平均BMD值明显高于Pp和pp 基因型(P< 0.05).结论 本研究结果提示ER-a基因PvuⅡ多态性直接影响蒙古族男性松质骨的骨峰值.     

过氧化物酶体增殖物激活受体γC161T基因多态性与糖皮质激素性骨质疏松症的关系

目的 探讨中国人过氧化物酶体增殖物激活受体γ(PPARγ)基因外显子6 C161T多态性与糖皮质激素性骨质疏松症(GIO)的相关关系。方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RELP)方法测定208例正常健康人（Ⅰ组）、168例非GIO患者（Ⅱ组）和104例GIO患者（Ⅲ组）PPARγ基因外显子6 C161T的基因型。应用双能X线骨密度仪(DEXA)测定股骨、腰椎等部位的骨密度。 结果 外显子6 C161T有CC、CT、TT 3种基因型。GIO组CC基因型频率显著低于正常对照组；CT和TT基因型频率显著高于正常对照组。非GIO组、应用激素组（GIO组＋非GIO组）与正常对照组比较，各基因型频率差异均无统计学意义。正常对照组C161T的CC基因型组各部位的骨密度有高于CT和TT基因型组的趋势，但差异无统计学意义。非GIO组和GIO组C161T的CC基因型组腰椎的骨密度明显高于CT和TT基因型组 (P ＜ 0.05)，分别为非GIO组CC型（1.04±0.17） g/cm2，CT+TT型（1.02±0.07） g/cm2；GIO组CC型（0.94±0.12） g/cm2，CT+TT型（0.83±0.08） g/cm2。经年龄、体重指数等因素校正后，差异仍有统计学意义(P ＜ 0.05）。 结论 PPARγ基因C161T基因型在正常人和应用激素患者之间无明显差异，它可能与肾小球肾炎的发病无关。C161T基因型在GIO组和正常对照组之间差异有统计学意义，它可能与糖皮质激素性骨质疏松症的发病有关。PPARγ基因C161T多态性与应用糖皮质激素患者腰椎的骨密度有关。等位基因C可能是骨量的保护因子，它可能与应用糖皮质激素后骨量的丢失有关。     

护骨素基因C1217T多态性与糖皮质激素性骨质疏松症的相关关系

目的：探讨我国应用糖皮质激素患者护骨素（osteoprotegerin,OPG）基因内含子C1217T单核苷酸多态性与糖皮质激素性骨质疏松症（glucocorticoid-induced osteoporosis,GIO）的相关性.方法：应用聚合酶链反应-限制性片断长度多态性（PCR-RELP）方法测定208例正常健康人（Ⅰ组）、168例非GIO患者（Ⅱ组）和104例GIO患者（Ⅲ组）护骨素基因内含子C1217T的基因型;应用双能X线骨密度仪（DEXA）测定股骨、腰椎等部位的骨密度.结果：内含子C1217T发现CC、CT、TT3种基因型,GIO组基因型CC频率显著低于正常对照组,CT和TT基因型频率显著高于正常对照组;非GIO组、应用激素组（GIO组＋非GIO组）与正常对照组比较各基因型频率均无统计学差异.正常对照组OPG基因C1217T的CC基因型组各部位的骨密度有高于CT和TT基因型组的趋势,但无统计学差异.非GIO组和GIO组OPG基因C1217T的CC基因型组腰椎的骨密度明显高于CT和TT基因型组（P＜0.05）,分别为：非GIO组CC（1.01±0.17）g/cm^2,CT＋TT（0.99±0.07）g/cm^2;GIO组CC（0.93±0.12）g/cm^2,CT＋TT（0.81±0.08）g/cm^2.经年龄、体重指数等因素校正后,差异仍有明显意义（P＜0.05）.结论：OPG基因C1217T基因型在正常人和应用激素患者（Ⅱ、Ⅲ组）之间无明显差异,它可能与肾小球肾炎的发病无关;C1217T基因型在GIO组和正常对照组之间有明显差异,它可能与糖皮质激素性骨质疏松症的发病有关;OPG基因C1217T多态性与应用糖皮质激素患者（Ⅱ、Ⅲ组）腰椎的骨密度明显相关,等位基因C可能是骨量的保护因子,它可能与应用糖皮质激素后骨量的丢失有关.     

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with osteoporotic vertebral fractures, but is a weak predictor of BMD

Osteoporosis is a common disease with a strong genetic component. Linkage studies have suggested linkage between BMD and loci on chromosome 1. The MTHFR gene is located on chromosome 1. MTHFR catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, which is used for homocysteine methylation to methionine. The rare genotype (TT) of the C677T polymorphism has previously been demonstrated to be associated with increased plasma homocysteine levels in individuals with inadequate plasma folate levels. Recently, the TT genotype has been found to be associated with reduced bone mass. We therefore examined if the C677T polymorphism in the MTHFR gene is associated with changes in bone mass and risk of osteoporotic fractures in 388 osteoporotic patients and 336 normal individuals. The distributions of the genotypes CC, CT and TT in women with osteoporotic vertebral fractures and normal controls were 43.5%, 42.2% and 14.3% and 52.0%, 42.0% and 8.0%, respectively, ²=5.62, P=0.06. Since studies of the functionality of this polymorphism have revealed that only the TT genotype is associated with biochemical changes, we also compared the prevalence of the TT genotype versus the CT- and CC genotypes in patients and controls and found that the TT genotype is significantly more common in women with vertebral fractures (14.3%) compared with normal controls (8.0%), ²=4.31, P<0.05. Logistic regression analysis demonstrated that vertebral fractures were significantly associated with BMD (lumbar spine) and height but only marginally with the MTHFR genotype (P=0.06). Multiple linear regression analysis revealed that weight, age and the MTHFR polymorphism were predictors of lumbar spine BMD in women. However, age- and gender-corrected BMD of the lumbar spine and the hip was not significantly different between MTHFR genotypes. Furthermore, individuals with the TT genotype did not have BMD significantly lower than the combined group of individuals with the CT- or CC genotypes. In conclusion, we have demonstrated that the rare TT genotype of the C677T polymorphism in the MTHFR gene is associated with increased risk of osteoporotic fractures in women and a weak predictor of lumbar spine BMD.     

Association of transforming growth factor beta1 genotype with therapeutic response to active vitamin D for postmenopausal osteoporosis.

Transforming growth factor beta (TGF-beta) is an important regulator of bone metabolism, its effects being intertwined with those of estrogen and vitamin D. A T-->C polymorphism in exon 1 of the TGF-beta1 gene, which results in the substitution of proline for leucine, is associated with bone mineral density (BMD). However, it is not known whether this polymorphism affects the response to treatment with active vitamin D or to hormone replacement therapy (HRT) in individuals with osteoporosis. Changes in BMD at the lumbar spine (L2-L4 BMD) were compared among TGF-beta1 genotypes in 363 postmenopausal Japanese women who were divided into three groups: an untreated, control group (n = 130), an active vitamin D treatment group (n = 117), and an HRT group (n = 116). TGF-beta1 genotype was determined with an allele-specific polymerase chain reaction assay. In the control group, the rate of bone loss decreased according to the rank order of genotypes TT (homozygous for the T allele) > TC (heterozygous) > CC (homozygous for the C allele), with a significant difference detected between the CC and TT genotypes. The positive response of L2-L4 BMD to HRT increased according to the rank order of genotypes TT < TC < CC, although the differences among genotypes were not statistically significant. Individuals with the CC genotype responded to active vitamin D treatment with an annual increase in L2-L4 BMD of 1.6%, whereas those with the TT or TC genotypes similarly treated lost bone to a similar extent as did untreated subjects of the corresponding genotype. These results suggest that TGF-beta1 genotype is associated with both the rate of bone loss and the response to active vitamin D treatment.     

Association of Transforming Growth Factor-b1 (TGFb1) T29?C Gene Polymorphism with Bone Mineral Density (BMD), Changes in BMD, and Serum Concentrations of TGF-b1 in a Population-Based Sample of Postmenopausal German Women

TGF-beta1 is thought to play an important role in bone turnover. Thus, the gene encoding TGF-beta1 is a prime candidate for the genetic regulation of bone density. Recent studies have suggested that a T29 --> C polymorphism in the signal sequence region of the TGF-beta1 gene may be related to bone mineral density (BMD) and bone loss in postmenopausal Japanese women. In the present study, we examined the relationship between this polymorphism and BMD in a population-based sample of 102 estrogen-deficient postmenopausal women from the Heidelberg cohort of the European Vertebral Osteoporosis Study (EVOS). Average BMD in women with the TT genotype was approximately 10% higher at both the lumbar spine and the femoral neck compared with women with the CC genotype (spine: 980 vs. 887 mg/cm2, P = 0.05; femoral neck: 755 vs. 674 mg/cm2; P = 0.02). Women with the TT genotype also experienced less overall bone loss at the total hip, compared with women with the CC genotype. Serum levels of TGF-beta1 were higher in women with the TT genotype than in those with the CC genotype (46.5 ng/ml vs. 32.3 ng/ml, P = 0.001). These data are clearly in contrast to findings in postmenopausal Japanese women where the CC genotype was associated with higher BMD and decreased bone loss. Further studies are therefore necessary to clarify the relationship between this polymorphism and BMD.     

Effects of the interaction between lean tissue mass and estrogen receptor alpha gene polymorphism on bone mineral density in middle-aged and elderly Japanese

Because both genetic and environmental factors influence bone mass, it is important to examine the effect of gene-environment interactions on bone mineral density (BMD) for the prevention of osteoporosis at an individual level. Estrogen receptor alpha (ER alpha) plays an important role in increasing BMD via mechanical strain and muscle mass is a reflection of the forces the muscle applies to the bone. The aim of this study is to investigate the effect of the interaction between lean tissue mass (LTM) and the ER alpha polymorphisms T-->C (PvuII) [dbSNP: rs2234693] and A-->G (XbaI) [dbSNP: rs9340799] on BMD in middle-aged and elderly individuals. Subjects were 2209 community-dwelling Japanese men and women, ages 40 to 79 years. ER alpha polymorphisms in the first intron, T-->C and A-->G were identified and lumbar spine and femoral neck BMD and LTM were measured by dual-energy X-ray absorptiometry. Both T-->C and A-->G polymorphisms were divided into two genotype groups (TT vs. TC/CC; AA vs. AG/GG). In postmenopausal women, the effect of LTM on femoral neck BMD was significantly larger for those with the TC/CC genotype than for those with the TT genotype for the T-->C polymorphism, and larger for those with the AG/GG genotype than for those with the AA genotype for the A-->G polymorphism. This gene-LTM interaction was observed at the femoral neck, but not at the lumbar spine. For men and premenopausal women, no gene-LTM interaction was found. In conclusion, there was an interaction between LTM and the ER alpha T-->C and A-->G polymorphisms with respect to their effect on femoral neck BMD in postmenopausal women and those with the TC/CC and AG/GG genotypes had larger effects of LTM than those with TT and AA genotypes.     

维生素D受体基因TaqⅠ多态性与绝经后妇女骨密度的关系

目的 了解福州地区绝经后妇女维生素D受体基因TaqⅠ多态性的分布,探讨维生素D受体基因TaqⅠ多态性与绝经后妇女骨密度的关系.方法 用双能X线骨密度仪检测592例绝经后妇女的腰椎、股骨颈、大转子和Wards三角骨密度,应用PCR-RFLP技术检测维生素D受体基因TaqⅠ多态性.结果 ①维生素D受体基因型分布频率为TT型90.37%,tt型0.17%,Tt型9.46%.等位基因频率为T 95.1%,t 4.9%,基因型分布符合Hardy-Weinberg定律.②分析其基因型与骨密度的关系:TT、tt、Tt 3种基因型在腰椎、股骨颈、大转子、Ward's区4个部位骨密度差异均无显著性.结论 维生素D受体基因TaqⅠ多态性与骨密度间无关联,不能作为预测福州地区绝经后妇女发生骨质疏松危险性的遗传标志.     

Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis

Transforming growth factor (TGF)-beta1 is the most abundant growth factor in human bone. It is produced by osteoblasts and inhibits osteoclast proliferation and activity and stimulates proliferation and differentiation of preosteoblasts. Several polymorphisms have been described in the TGF-beta1 gene. Previously, we and others have found associations between some of these polymorphisms and bone mass. We therefore wanted to examine if these polymorphisms are also predictors of osteoporotic fractures. The polymorphisms G(-1639)-A, C(-1348)-T, C(-765)insC, T(29)-C, G(74)-C, 713-8delC, C(788)-T, and T(816-20)-C were examined using RFLP and sequencing in 296 osteoporotic patients with vertebral fractures and 330 normal individuals. Bone mineral density (BMD) was examined at the lumbar spine and at the femoral neck by DXA. Genotype distributions were in H-W equilibrium. Linkage disequilibrium was found between the polymorphisms. The T(816-20)-C genotypes were distributed differently among osteoporotic patients and normal controls. The TT genotype was less common in individuals with osteoporotic fractures (chi(2) = 6.02, P < 0.05). BMD was higher in individuals with the TT-genotype (T(816-20)-C) at the lumbar spine, 0.960 +/- 0.173 g/cm(2) compared with individuals with the TC or CC genotypes: 0.849 +/- 0.181 g/cm(2) and 0.876 +/- 0.179 g/cm(2), respectively (P < 0.001, ANOVA). Similar differences between genotypes were found at the different hip regions as well as at the total hip. Individuals with the TT-genotype (C(-1348)-T) had higher bone mass at the femoral neck: 0.743 +/- 0.134 g/cm(2) compared with 0.703 +/- 0.119 g/cm(2) in individuals with TC or CC genotypes (P < 0.05). Individuals with the CC-genotype (T(29)-C) had higher bone mass at the femoral neck, 0.735 +/- 0.128 g/cm(2) compared with 0.703 +/- 0.120 g/cm(2) in individuals with TC or TT genotypes (P < 0.05) and at the total hip: 0.852 +/- 0.166 g/cm(2) vs. 0.818 +/- 0.149 g/cm(2), respectively (P < 0.05). None of the other polymorphisms were distributed differently in patients and controls and did not affect BMD. In conclusion, The TT genotype of the T(816-20)-C polymorphism is less common in patients with osteoporotic fractures and is associated with higher bone mass both at the lumbar spine and at the hip. The C(-1348)-T and T(29)-C polymorphisms were distributed similarly in osteoporotic patients and normal controls, however, the rare genotypes were associated with higher bone mass at the hip.     

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.     

Interleukin-6 gene polymorphism is related to bone mineral density during and after puberty in healthy white males: a cross-sectional and longitudinal study.

Bone mineral density (BMD) is under strong genetic control and is the major determinant of fracture risk. The cytokine interleukin-6 (IL-6) is an important regulator of bone metabolism and is involved in mediating the effects of androgens and estrogens on bone. Recently, a G/C polymorphism in position -174 of the IL-6 gene promoter was found. We investigated this genetic polymorphism in relation to BMD during late puberty and to peak bone mass, in healthy white males. We identified the IL-6 genotypes (GG, GC, and CC) in 90 boys, age 16.9 +/- 0.3 years (mean +/- SD), using polymerase chain reaction (PCR). BMD (g/cm2) at the femoral neck, lumbar spine, and total body was measured using dual energy X-ray absorptiometry. The volumetric BMD (vBMD; mg/cm3) of the lumbar spine was estimated. Differences in BMD in relation to the genotypes were calculated using analysis of variance (ANOVA). Subjects with the CC genotype had 7.9% higher BMD of the femoral neck (p = 0.03), 7.0% higher BMD of the lumbar spine (p < 0.05), and 7.6% higher vBMD of the lumbar spine (p = 0.04), compared with their GG counterparts. Using multiple regression, the IL-6 genotypes were independently related to total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p < 0.05), neck BMD (CC > GG; p = 0.01), spine BMD (CC > GG; p = 0.01), and spine vBMD (CC > GG; p = 0.008). At age 19.3 +/- 0.7 years (mean +/- SD; 88 men) the IL-6 genotypes were still independent predictors for total body BMD (CC > GG; p = 0.03), humerus BMD (CC > GG; p = 0.03), spine BMD (CC > GG; p = 0.02), and spine vBMD (CC > GG; p = 0.003), while the IL-6 genotypes were not related to the increase in bone density seen after 2 years. We have shown that polymorphism of the IL-6 gene is an independent predictor of BMD during late puberty and of peak bone mass in healthy white men.