骨保护素基因启动子T950C和T245G多态性与骨质疏松症相关性的Meta分析
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摘要
目的：系统评价OPG基因启动子T950C及T245G多态性与骨质疏松症的关联性。
方法：利用计算机系统检索1996年至2011年2月Medline、Embase、中国知网、万方及维普数据库并结合手工检索获取OPG基因启动子T950C及T245G多态性与骨质疏松症的关联性的文献。根据纳入及排除标准获取和剔除文献,利用Jadad评分表评价纳入文献的质量,并提取纳入文献的相关数据,使用RevMan5.0软件进行Meta统计分析,根据文献间的异质性结果选择固定或随机效应模型进行数据合并,采用倒漏斗图及Begg法评估发表偏倚,对各研究结果进行敏感性分析,评价Meta分析结果的稳定性。
结果：通过筛选所检索到的文献,共16篇文献纳入本Meta中,其中涉及T950C的文献11篇,累计样本量4507人,研究人群来源于6个国家；涉及T245G的文献9篇,累计样本量3717人,研究人群来源于5个国家。
OPG基因启动子T950C的Meta分析结果发现：1.TT基因型脊柱BMD均明显小于TC、CC基因型的BMD,而TC基因型脊柱BMD与CC基因型的BMD无明显相关性,对地域行分层分析发现亚洲组TT基因型脊柱BMD均小于TC、CC基因型的BMD,而欧洲组各基因型之间脊柱BMD无明显相关性；2.各基因型在股骨颈BMD研究中呈现出TT OPG基因启动子T245G的Meta分析结果发现：1.TT基因型脊柱BMD明显大于GG基因型BMD；而对股骨颈BMD研究发现各基因型BMD无明显相关性；2.由于GG基因型数量较少,故将TG与GG合并与TT的BMD相比发现TT基因型在脊柱和股骨颈BMD中均大于TG+GG型的BMD; 3. G等位基因骨质疏松发病率较正常组发病率高,而T等位基因骨质疏松发病率较正常组发病率低。
结论：OPG基因启动子T950C和T245G多态性与骨密度及骨质疏松的发病都有密切相关性,是骨质疏松症的易感基因,可以用来作为骨质疏松症危险性研究的遗传学标志。
Objective:To systematically evaluate the relation of T950C and T245G polymorphism in osteoprotegerin gene promoter and Osteoporosis.
Methods:Literature were retrieved by computerized searching from Medline,Embase,CNKI, wangfang and VIP databases combined with manual searches of T950C and T245G polymorphism in osteoprotegerin gene promoter and Osteoporosis between 1996 and 2011. Literature were accessed and removed by Inclusion and exclusion criteria, included evaluate the quality of the literature by jadad score table and extract the data from literature.The statistical analysis was conducted by RevMan5.0 software.The fixed or random effect model was chosen according to the heterogeneity between the literature to merge the data. The publication bias and stability of analysis were evaluated by using funnel plot and Begg method and sensitivity analysis.
Results:A total of 16 studies were included into the review,of which 11 studies related to T950C, the total sample size of 4507 from six countries; of which 9 studies related to T245G, total sample size of 3717 from five countries.
The result of Meta-analysis of osteoprotegerin gene promoter T950C:1.TT genotype were found to have significantly lower spine BMD than TC and CC genotype, while no significant relation between TC and CC. The Asian Group of TT genotype were found to have significantly lower spine BMD than TC and CC genotype,while no significant relation in European Group. 2.The relationship between genotype and femoral neck BMD showed TT The result of Meta-analysis of osteoprotegerin gene promoter T245G:1.TT genotype were found to have significantly lower spine BMD than GG genotype, while no significant relation was found between T245G and femoral neck BMD.2. TT genotype were found to have significantly higher spine BMD and femoral neck BMD than TG+GG genotype.3. Allele G was found to have significantly higher in osteoporosis group than normal group,while Allele T was found to have significantly lower in osteoporosis group than normal group.
Conclusions:T950C and T245G polymorphism in osteoprotegerin gene promoter are associated with BMD and osteoporosis,which can be the susceptible gene of osteoporosis and an useful genetic maker for studies on BMD and osteoporosis.
方法：利用计算机系统检索1996年至2011年2月Medline、Embase、中国知网、万方及维普数据库并结合手工检索获取OPG基因启动子T950C及T245G多态性与骨质疏松症的关联性的文献。根据纳入及排除标准获取和剔除文献,利用Jadad评分表评价纳入文献的质量,并提取纳入文献的相关数据,使用RevMan5.0软件进行Meta统计分析,根据文献间的异质性结果选择固定或随机效应模型进行数据合并,采用倒漏斗图及Begg法评估发表偏倚,对各研究结果进行敏感性分析,评价Meta分析结果的稳定性。
结果：通过筛选所检索到的文献,共16篇文献纳入本Meta中,其中涉及T950C的文献11篇,累计样本量4507人,研究人群来源于6个国家；涉及T245G的文献9篇,累计样本量3717人,研究人群来源于5个国家。
OPG基因启动子T950C的Meta分析结果发现：1.TT基因型脊柱BMD均明显小于TC、CC基因型的BMD,而TC基因型脊柱BMD与CC基因型的BMD无明显相关性,对地域行分层分析发现亚洲组TT基因型脊柱BMD均小于TC、CC基因型的BMD,而欧洲组各基因型之间脊柱BMD无明显相关性；2.各基因型在股骨颈BMD研究中呈现出TT
结论：OPG基因启动子T950C和T245G多态性与骨密度及骨质疏松的发病都有密切相关性,是骨质疏松症的易感基因,可以用来作为骨质疏松症危险性研究的遗传学标志。
Objective:To systematically evaluate the relation of T950C and T245G polymorphism in osteoprotegerin gene promoter and Osteoporosis.
Methods:Literature were retrieved by computerized searching from Medline,Embase,CNKI, wangfang and VIP databases combined with manual searches of T950C and T245G polymorphism in osteoprotegerin gene promoter and Osteoporosis between 1996 and 2011. Literature were accessed and removed by Inclusion and exclusion criteria, included evaluate the quality of the literature by jadad score table and extract the data from literature.The statistical analysis was conducted by RevMan5.0 software.The fixed or random effect model was chosen according to the heterogeneity between the literature to merge the data. The publication bias and stability of analysis were evaluated by using funnel plot and Begg method and sensitivity analysis.
Results:A total of 16 studies were included into the review,of which 11 studies related to T950C, the total sample size of 4507 from six countries; of which 9 studies related to T245G, total sample size of 3717 from five countries.
The result of Meta-analysis of osteoprotegerin gene promoter T950C:1.TT genotype were found to have significantly lower spine BMD than TC and CC genotype, while no significant relation between TC and CC. The Asian Group of TT genotype were found to have significantly lower spine BMD than TC and CC genotype,while no significant relation in European Group. 2.The relationship between genotype and femoral neck BMD showed TT
Conclusions:T950C and T245G polymorphism in osteoprotegerin gene promoter are associated with BMD and osteoporosis,which can be the susceptible gene of osteoporosis and an useful genetic maker for studies on BMD and osteoporosis.
引文
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[2]No authors listed.Osteoporosis prevention,diagnosis and therapy[J]. NIH Consens Statement,2000,17(1):1-45.
[3]Amizuka N,Shimomura J,Li M,et al.Defective bone remodelling in osteoprotegerin defcient mice[J].Electron Microsc.2003;52:503-13.
[4]刘关键,吴泰相Meta-分析的森林图及临床意义[J].中国循证医学杂志,2004,(03)：198-201.
[5]单春艳,郑少雄,陈莉明.绝经后骨质疏松妇女全血细胞分泌某些细胞因子水平的改变[J].现代康复,2001,(18)：104-105.
[6]Bord S,Beavan S,Ireland D,et al.Mechanisms by which high-dose estrogen therapy produces anabolic skeletal effects in postmenopausal women:role of locally produced growth factors. Bone.2001 Sep;29(3):216-22.
[7]Carson DS.Menopause and osteoporosis:the role of HRT.J Am Pharm Assoc (Wash).1996 Apr;NS36(4):234-242,269.
[8]Nakayama H.Active vitamin D3 therapy for gulucocorticoid-induced osteoporosis.Clin Calcium.2006 Jul;16(7):1201-7.
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[20]Lubahn DB,Moyer JS,Golding TS,et al.Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc Natl Acad Sci USA.1993 Dec 1;90(23):11162-6.
[21]Matsushita H,Kurabayashi T,Tomita M,et al.Effects of vitamin D and estrogen receptor gene polymorphisms on the changes in lumbar bone mineral density with multiple pregnancies in Japanese women.Hum Reprod.2004 Jan;19(1):59-64.
[22]Langdahl BL,Knudsen JYJensen HK,et al.A sequence variation:713-8de1C in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women.Bone.1997 Mar;20(3):289-94.
[23]Yamada Y,Miyauchi A,Goto J,et al.Association of a polymorphism of the transforming growth factor-betal gene with genetic susceptibility to osteoporosis in postmenopausal Japanese women. J Bone Miner Res.1998 Oct; 13(10):1569-76.
[24]Grant SF,Reid DM,Blake G,etal. Reduced bone density and osteoporosis associated with a polymorphic Spl binding site in the collagen type I alpha 1 gene.Nat Genet.1996 Oct;14(2):203-5.
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