Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
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DOI：
10.1007/s00198-007-0512-z
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发表时间：
2008-06-01
影响因子：
4
通讯作者：
Akesson, K.
中科院分区：
文献类型：
--
作者：
Grundberg, E.;Lau, E. M.;Akesson, K.
在此，我们研究了LRP 5基因多态性与骨表型和骨折之间的关系，在三个大型男性队列的基础上，LRP 5突变导致严重的骨表型。结果显示Val 667 Met SNP与脊柱BMD在3，800年轻和老年男子.Introduction低密度脂蛋白受体相关蛋白5（LRP 5）-Wnt信号系统是调节成骨细胞活性的重要性，这变得清晰后，发现失活突变LRP 5导致骨质疏松症。本研究的总体目的是调查LRP 5基因多态性与三个大型队列的年轻和老年男性骨密度（BMD）之间的关联。（n = 3014，年龄69-81岁）和MrOs香港（n = 2000，年龄> 65岁）和瑞典GOOD研究（n = 1068，年龄18 - 20岁）。采用TaqMan分析法对多态性Val 667 Met和Ala 1330 Val进行基因分型。结果在一项荟萃分析（n = 3，800）中，将来自瑞典队列的数据结合起来，携带667 Met等位基因的男性腰椎BMD比非携带者低3%（p < 0.05）。Val 667 Met SNP在香港人群中不具有多态性，因此未纳入。在研究人群中，Ala 1330 Val SNP与骨表型之间没有关联。LRP 5多态性和自我报告的骨折之间没有关联被认为是在MrOs Sweden.Conclusions从这三个大的队列结果表明，Val 667 Met多态性，但不是Ala 1330 Val有助于观察到的变化，在瑞典人群的BMD。
Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men.Introduction The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men.Methods The cohorts used were MrOS Sweden (n = 3014, aged 69-81 years) and MrOs Hong Kong (n = 2000, aged > 65 years) and the Swedish GOOD study (n = 1068, aged 18 20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay.Results When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden.Conclusions Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.