ER基因多态性与中国南方妇女绝经后骨质疏松症的病例-对照研究

目的对中国南方绝经后妇女中雌激素受体基因PvuⅡ和XbaⅠ核酸限制性内切酶多态性与骨质疏松症的关系进行了病例一对照调查。方法中国南方绝经后妇女182人，分为骨质疏松组和正常对照组，每组91人；均用DEXA检测骨密度，用PCR—RFLP的方法鉴定雌激素受体的基因型，分析雌激素受体基因多态性与骨密度的关系及各基因型在骨质疏松组与对照组的分布。结果PP、xx、Ppxx、PPxx型在骨质疏松组中的分布频率高于正常对照组，差异有统计学意义。PP、xx、Ppxx、PPxx四种基因型的携带者比正常人骨质疏松的易患程度分别高2．46、2．972、2．2、15倍。结论可以将ER基因PvuⅡ和XbaⅠ多态性作为在中国南方进行筛选绝经后骨质疏松症的高危人群的依据之一。     

绝经后骨质疏松症相关基因多态性的研究进展

国内外学者对骨质疏松症的遗传机制已开展了大量的研究,试图寻找与其发生密切相关的致病基因,从而揭示其遗传机制.在复习绝经后骨质疏松症相关文献的基础上,本文对雌激素受体基因、维生素D受体基因及I型胶原基因等相关基因多态性进行综述,发现相关文献报道虽多,但研究结果争议较多,尚不能达成共识.认为骨质疏松症不太可能是由个别基因的主要效应导致,而应该由多个基因分别产生微效应来决定;且已发现的这些基因可能占所有与其相关基因的4%还不到,尚有许多与之相关的基因未被发现及重视.近年来,全基因组关联研究结果以及今后类似的研究已为骨质疏松症的基因学研究开启了一片新天地.     

福州地区绝经后妇女骨钙素基因Hind Ⅲ多态性与骨密度的关系

目的 探讨绝经后妇女骨钙素基因(OC)Hind Ⅲ多态性与骨密度的关系.方法 用双能X线骨密度仪检测247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OC基因Hind Ⅲ多态性.结果 ①OC基因型分布频率为HH型4.9%,hh型49%,Hh型46.1%.等位基因频率为H 27.94%,h 72.06%,基因型分布符合Hardy-Weinberg定律.②HH基因型与hh型在股骨颈、大转子、Wards三角区骨密度有显著性差异(P<0.05);HH基因型与Hh型在大转子、Wards三角区骨密度也有显著性差异(P<0.05).③有h等位基因的股骨颈、大转子、Wards三角区骨密度显著低于无h等位基因(P<0.05).结论 福州地区绝经后妇女OC基因多态性与骨密度存在相关性,有h等位基因绝经后妇女在股骨颈、大转子、Wards三角区有低骨密度风险.     

ER基因多态性与中国南方妇女绝经后骨质疏松的病例对照研究

[目的]对中国南方绝经后妇女中雌激素受体基因PvuⅡ和XbaⅠ核酸限制性内切酶多态性与骨质疏松症的关系进行了病例一对照调查。[方法]研究对象总共182名中国南方绝经后妇女，研究对象均用DEXA检测骨密度，用PCR-RFLP的方法鉴定雌激素受体的基因型，分析雌激素受体基因多态性与骨密度的关系及各基因型在骨质疏松组与对照组的分布。[结果]PP、xx、Ppxx、PPxx型在骨质疏松组中的分布频率高于正常对照组，差别有统计学意义。PP、XX、Ppxx、PPxx4种基因型的携带者比正常人骨质疏松的易患程度分别高2．46、2．972、2．2、15倍。[结论]可以将ER基因PvuⅡ和XbaⅠ多态性作为在中国南方进行筛选绝经后骨质疏松症的高危人群的依据之一。     

降钙素受体基因多态性与中国绝经后妇女骨密度的Meta分析

目的系统评估降钙素受体(CRT)基因多态性与中国绝经后妇女骨密度的关系。方法计算机检索Pubmed、Embase、Web of science、Cochrane library、中国知网(CNKI)、维普(VIP)、万方数据库及中国生物医药文献数据库(CBD),收集有关CRT基因多态性与中国绝经后妇女骨密度的关系的文献,按照纳入和排除标准筛选文献并提取数据,采用Rev Man5.3、Stata12.0软件进行Meta分析,计算合并加权均数差(WMD)值和95%CI,并采用Begg检验和Egger检验进行发表偏倚评价,逐一排除法进行敏感性分析。结果共纳入7篇文献,累计病例1702例。Meta分析结果显示CRT基因多态性与北方绝经后妇女L2-4、大转子、Ward三角骨密度有关(P0.05),与南方绝经后妇女大转子骨密度有关(P0.05)。北方绝经后妇女CRT CC基因型大转子处骨密度较高(CC vs CT:WMD=0.05,95%CI=0.03~0.08,P0.00001;CC vs CT+TT:WMD=0.04,95%CI=0.01~0.07,P=0.003),南方绝经后妇女CRT CC基因型大转子处骨密度则相反(CC vs CT:WMD=-0.35,95%CI=-0.66~-0.03,P=0.03;CC vs CT+TT:WMD=-0.36,95%CI=-0.67~-0.05,P=0.02)。结论 CRT基因多态性可能与中国绝经后妇女骨密度有关,可作为预测骨质疏松和骨折风险的遗传指标。     

绝经后健康妇女雌激素受体基因多态性与骨密度关系的研究

目的从分子生物学水平探讨中国绝经后健康妇女雌激素受体（ＥＲ）基因多态性与骨密度的关系。方法选择绝经后健康、无亲缘关系妇女２３７例，运用双能Ｘ线吸收骨密度仪及聚合酶链反应——限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）方法分析ＥＲ基因多态性与骨密度的关系。结果２３７例绝经后健康妇女中ＰＰ、Ｐｐ及ｐｐ基因型频率分别为０．１９８，０．４４３及０．３５９；Ｐ与ｐ等位基因频率分别为０．４１９８、０．５８０２。方差分析（ＡＮＯＶＡ）显示股骨大转子部位骨密度与ＥＲ基因多态性相关（ｐ＝０．０１０６），ＰＰ基因型各部位骨密度值均低于Ｐｐ、ｐｐ基因型。逐步多元回归分析发现ＥＲ基因多态性与股骨大转子（ｐ＝０．０５４８）及腰椎２－４（Ｐ＝０．０９９８）部位的骨密度相关。结论中国绝经后健康妇女ＥＲ基因多态性与股骨大转子部位的骨密度显著相关，ｐ等位基因具有一定的骨量保护作用，提示从分子水平探讨骨量丢失规律以及防治骨质疏松症的发生发展具有一定的现实意义。     

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.     

MTHFR基因多态性与蒙古族绝经后妇女骨质疏松的相关性研究

目的探讨本地区蒙古族绝经后妇女亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因的多态性位点C677T、A1298C基因多态性与内蒙古地区蒙古族绝经后女性骨质疏松症(osteoporosis,OP)遗传易感性的关系。方法收集150例门诊及住院(确诊为骨质疏松)蒙古族绝经后妇女为观察组,对照组来自门诊按年龄配比的骨含量正常的蒙古族绝经后妇女145例,均以双能X线骨密度仪测定腰椎和髋部骨密度,以T值≤-2.5诊断为骨质疏松,-2.5≤T≤-1.0为骨含量减少,T值-1.0为骨含量正常,并进行MTHFR C677T及A1298C基因多态性检测。结果骨质疏松组MTHFR基因受体C677T基因型CC、CT、TT频率分别为29.3%、44.0%和27.7%,对照组基因型CC、CT、TT频率分别为42.8%、44.8%和12.4%,两组差异有统计学意义(P=0.017)。骨质疏松症组中的T等位基因频率为48.7%,显著高于对照组(34.8%,P=0.005),提示T等位基因是骨质疏松发生的危险因素(OR=1.77,95%CI=1.18~2.64,P=0.001)。与CC基因型相比,TT基因型携带者的骨质疏松发生风险增加至3.15倍(95%CI=1.45~6.86,P=0.004),该作用在年龄≥60岁及体重指数偏高的女性中表现更明显。而MTHFR A1298C的多态性位点对绝经后骨质疏松的发生没有显著影响(P=0.513)。结论 MTHFR C677T基因变异与蒙古族绝经后妇女骨质疏松易感性明显相关,MTHFR A1298C的多态性位点与蒙古族绝经后妇女骨质疏松的发生没有明显相关性。     

FSHR基因多态性与绝经后骨质疏松症的关联性分析

目的探讨卵泡刺激素受体(FSHR)中外显子10多态性与绝经后骨质疏松症的相关性。方法选取2017年8月至2019年3月因骨质疏松于本院骨科住院的136例绝经后女性患者为研究对象(骨质疏松组),同期选取118例绝经后非骨质疏松女性作为对照(对照组)。提取两组女性外周血基因组DNA,采用PCR法扩增FSHR基因外显子10的片段并进行基因测序,探究其基因多态性。结果两组年龄、绝经期年龄、绝经期年限、糖尿病患病比例、高血压患病比例、糖化血红蛋白(Hb A1c)、空腹胰岛素(FINS)比较,差异无统计学意义(P0.05);骨质疏松组抗酒石酸酸性磷酸酶-5b(TRACP-5b)、血清骨碱性磷酸酶(BALP)水平显著高于对照组,体质量指数(BMI)、腰椎骨密度(BMD)、股骨颈BMD水平显著低于对照组,差异有统计学意义(P0.05); FSHR在基因外显子10的680多态位点上有A/A型、A/S型、S/S型3种基因型,对照组基因型中A/A型(占62.71%)最多,其次为A/S型(占20.33%),S/S型(占16.96%)最少;骨质疏松组基因型中以S/S型(占59.56%)为主,其次为A/A型(占28.68%),A/S型(占11.76%)最少,两组基因型比较,差异均有统计学意义(P0.05); S/S型基因型、BMI是影响骨质疏松发生的独立危险因素,腰椎L2-L4 BMD、股骨颈BMD是影响骨质疏松发生的保护因素(P0.05)。结论FSHR基因多态性与绝经后骨质疏松症有一定相关性,其中S/S型基因型在绝经后骨质疏松患者中出现频率较高,可能与绝经后骨质疏松发生发展有关。     

降钙素受体rs1801197基因多态性与骨质疏松症相关性的Meta分析

目的 系统评价降钙素受体基因多态性与骨质疏松症的关系.方法 计算机检索知网、万方、CBM、PubMed和Embase数据库,搜集CTR基因多态性与骨质疏松症相关性的文献,检索时限从建库至2020年10月.由两名研究者分别独立按照纳入与排除标准筛选文献并提取数据,采用Stata11.0软件进行统计学分析,计算OR值和95...     

Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women.

Leptin is emerging as a key regulator of bone remodeling. In a population-based study of 1306 postmenopausal Danish women, nonsynonymous LEPR SNPs were associated with risk of adiposity, BMD, and vertebral fracture. Smoking exacerbates this LEPR-associated fracture risk. INTRODUCTION: Nonsynonymous single nucleotide polymorphisms (SNPs) in the human LEPR gene have been associated with adiposity in a number of studies, but there have been no large-scale studies of their implications for BMD and osteoporotic fracture risk in postmenopausal women. MATERIALS AND METHODS: We carried out a population-based study of 1430 women. Three well-known nonsynonymous leptin receptor (LEPR) SNPs (Lys109Arg, Gln223Arg, and Lys656Asn) were genotyped for qualitative and quantitative association analysis. Phenotype characteristics of main interest were DXA measures of body fat and lean tissue mass, BMD, and radiographic vertebral fractures. RESULTS: Gln223Arg associated with risk of vertebral fracture (overall OR = 1.76; OR in smokers = 2.31; p = 0.0004), in addition to BMD of the femoral neck and total hip (p = 0.036 and 0.008, respectively). Heterozygote carriers showed lower BMD at both sites. Gln223Arg was also associated with adiposity (p = 0.001 for total fat mass). For adiposity, the at-risk allele was G (resulting in an arginine at position 223). CONCLUSIONS: Variation in LEPR seemed to contribute to the variation in BMD and fracture risk in Danish postmenopausal women; the heterozygous genotype was associated with increased risk of manifest osteoporosis. Further studies are needed to replicate these data and to clarify the mechanisms involved.     

安徽地区绝经后妇女雌激素受体基因多态性与骨密度的相关性研究

目的探讨安徽地区绝经后妇女雌激素受体（ER）基因多态性的分布及其与骨密度的相关性。方法随机选择288名安徽合肥地区健康绝经后妇女，运用双能X线骨密度吸收法（DEXA）测定腰椎和股骨颈、大转子骨密度（BMD），并采用PCR-RFLP（聚合酶链反应-限制性片断长度多态性）法分析ER基因多态性，并分析其相关性。结果安徽地区绝经后妇女ER基因型分布频率PP（13．2％）、Pp（45．8％）、pp（40．9％），XX（5．21％）、Xx（31．6％）、xx（63．2％），联合PvuⅡ和XbaⅠ这两种基因型后得到：PPXX（5．6％），PPXx（3．8％），PPxx（6．3％），PpXX（1．4％），PpXx（23．3％），Ppxx（25％），ppxx（34．7％），未检测到ppXX及ppXx型。PvuⅡ多态性与绝经后妇女腰椎BMD相关，PP基因型腰椎BMD显著低于pp和Pp基因型（P〈0．05），ER基因P等位基因是一种有益于骨量的基因型。XbaⅠ多态性与绝经后妇女各部位BMD间无明显相关性（P〉0．05）。联合分析PvuⅡ和XbaⅠ多态性与绝经后妇女BMD相关性发现，有Px单倍型的妇女腰椎部位的BMD显著低于无此单倍型的妇女（P〈0．01）。结论ER基因PVuⅡ多态性与绝经后妇女腰椎BMD有相关性，PP基因型妇女腰椎BMD减低，而具有Px单倍型的ER基因可能对BMD有不利影响。     

Estrogen receptor gene polymorphism and bone mineral density in postmenopausal Chinese women

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) for the estrogen receptor gene (ERG) and its relation to bone mineral density (BMD) were examined in 454 postmenopausal Chinese women, aged 55-79 years. The RFLPs were represented as P or p (PvuII) and X or x (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. There was no significant difference in BMD between the PP, Pp, and pp genotypes. However, women of the XX genotype had significantly higher BMD at the spine than women of the Xx or xx genotype. The magnitude of the difference in BMD was 80% of a standard deviation (SD) for BMD in elderly women and 40% of a SD in postmenopausal women. There was no statistically significant interaction between the PvuII genotype and the XbaI genotype in determining BMD. We conclude that postmenopausal Chinese women who were homozygous for the XX genotype had slightly higher BMD than the others. However, the difference in BMD was small and was unlikely to have any clinical significance. The ERG is not a major determinant of BMD in Chinese women in Hong Kong.     

Association between leptin receptor gene polymorphisms and early-onset prostate cancer

OBJECTIVE: To report a case-control study examining the relationship between polymorphisms in the leptin receptor (OBR) gene and the development of young-onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS: The Lys109Arg (OBR1) and Gln223Arg (OBR2) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS: There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65-2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58-1.26), but neither was statistically significant. CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK.     

Association between X-ray repair cross-complementing group 1 Arg399Gln polymorphism and male infertility: An update meta-analysis

Numerous studies concentrate on the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphism and male infertility; however, the results remain inconclusive and inconsistent. Hence, this meta-analysis was conducted to get a precise estimation of the correlation. PubMed, Web of Science, Embase, Scopus and China National Knowledge Infrastructure (CNKI) databases were searched to identify the all relevant studies before 3 May 2020. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the strength of the association. Finally, six studies with 1,886 cases and 1,212 controls were included in our study. The result indicated that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility under allelic model (A-allele vs. G-allele: OR = 1.183, p = .003), heterozygote genetic model (AA vs. GA: OR = 1.256, p = .027), recessive genetic model (AA vs. GG + GA: OR = 1.279, p = .012) and dominant genetic model (AA + GA vs. GG: OR = 1.218, p = .026). In addition, in Asian subgroup, statistic correlation remained significant in allelic model (A-allele vs. G-allele: OR = 1.145, p = .025) with rare heterogeneity (I² = 0%). In summary, our meta-analysis suggested that XRCC1 Arg399Gln polymorphism was significantly associated with male infertility and the A-allele might be a risk factor for this disease, especially in Asians.     

绝经后妇女膝关节骨性关节炎和骨质疏松症发生率关系

目的研究分析绝经后妇女骨质疏松症和膝关节骨性关节炎发生率关系。方法回顾性分析100例绝经后骨质疏松患者以及100例绝经后骨关节炎患者的基本资料,对患者的年龄、体重指数进行计算,做好骨密度的测定,对两组患者的骨质疏松以及骨关节炎等指标的变化进行比较。结果观察A组中的100例骨质疏松患者88例为II度以上的骨性关节炎。同时观察B组中的100例骨性关节炎患者中25例腰椎和髋部骨密度逐渐下降,其T值小于-2.5SD,确诊为骨质疏松症。随着年龄的增长,绝经后妇女骨质疏松和骨质增生伴发率逐渐增加,同时绝经后妇女的体重指数和骨密度以及骨关节炎有着正相关的关系,绝经后妇女骨质疏松体重指数较大的,并合并骨性关节炎患者的发生率逐渐增加,骨性关节炎患者体重指数较低,骨质疏松发生的可能性较大。结论绝经后妇女骨质疏松和骨性关节炎的发生,和年龄有密切的关联,同时骨性关节炎是骨质疏松症发生的一种重要影响因素。     

Osteogenic potential and responsiveness to leptin of mesenchymal stem cells between postmenopausal women with osteoarthritis and osteoporosis

The aim of this study was to compare the osteogenic potential and responsiveness to leptin of mesenchymal stem cells (MSCs) from bone marrow between postmenopausal women with osteoarthritis (OA) and osteoporosis (OP). MSCs of the proximal femur from OA and OP donors were cultured under control and different experimental mediums. After verifying the availability of primary cells, their osteogenic potential and responsiveness to leptin were compared between two groups. Similar patterns of cell growth were shown in both OA and OP groups. However, after the sixth passage, the viability of undifferentiated cells decreased more in OP than in OA donors. Under the same osteogenic supplements condition, the mRNA expression of osteogenesis‐specific genes, osteocalcin (OC) and alkaline phosphatase (ALP) were higher in OA group. Comparison of bone matrix mineralization was parallel to that of mRNA expression. The level of bone‐specific ALP (BAP) was higher in cells from donors with OA, whereas osteoprotegerin (OPG) was higher in OP group. This difference in BAP expression proved to be insignificant after the administration of leptin. Although leptin upregulated the expression of OPG, a significant difference still existed between OA and OP. In conclusion, differential osteogenic potential and responsiveness to leptin of MSCs were noted between postmenopausal women with OA and OP. Differential biological behavior of MSCs seems to be partly related to the different distribution of bone mass between OA and OP populations. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1067–1073, 2009