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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites.
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Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites.

机译：低密度脂蛋白受体相关蛋白5（LRP5）基因多态性与中国人和白人的骨量有关。

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In this study, the associations of novel LRP5 variants with BMD variation were detected and some replicated in the two ethnic groups of Chinese and white origins, respectively. These data support the concept that LRP5 variation can contribute to minor and major variation in bone structure. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been shown to cause both high and low bone mass. However, it is still controversial whether LRP5 is associated with normal BMD variation. This study explored the association of LRP5 with BMD phenotypes at three clinically important skeletal sites-the spine, hip, and ultradistal radius (UD)-in two independent populations of Chinese and white ethnicities, respectively. MATERIALS AND METHODS: The Chinese sample consisted of 733 unrelated subjects. The white sample was made up of 1873 subjects from 405 nuclear families. High-density single nucleotide polymorphisms (SNPs) across the whole LRP5 gene were genotyped and analyzed in both samples. RESULTS: Linkage disequilibrium (LD) analyses showed that the haplotype structures of LRP5 between Chinese and whites were in good agreement. Association tests showed that polymorphisms in block 5 spanning intron 7 to intron 19 of LRP5 significantly associated with spine BMD variation in both samples. Particularly, the significant association of SNP rs491347 in intron 7 with spine BMD in the Chinese sample (p=0.002) was replicated in whites, even after adjusting for multiple testing (p=0.005). Its strongly associated SNP rs1784235 could cause the loss of an estrogen receptor alpha (ERalpha) binding site in LRP5, which could partially explain the above replicated association. However, we did not observe any significant replication with BMD variation at the hip and UD. After accounting for multiple testing, associations with BMD variation at these two sites were mainly found in Chinese. Sex-stratified analyses further revealed that the LRP5 associations with BMD in Chinese and whites were driven by male and female subjects, respectively. CONCLUSIONS: Our work supported LRP5 genetic variants as possible susceptibility factors for osteoporosis and fractures in humans. Especially, the SNP rs491347 and its strongly associated SNPs (e.g., rs1784235) could be important to human osteoporosis phenotypes.
机译：在这项研究中，新的LRP5变异与BMD变异的关联被检测到，并且分别在华裔和白人两个族群中复制。这些数据支持LRP5变异可能导致骨骼结构发生细微变化的概念。引言：低密度脂蛋白受体相关蛋白5（LRP5）基因的突变已显示会导致高和低的骨量。但是，LRP5是否与正常的BMD变化有关仍存在争议。这项研究探索了在三个临床上重要的骨骼部位（脊柱，髋部和超dist半径（UD））的LRP5与BMD表型的关系，分别位于两个独立的中国人和白人。材料与方法：中国样本包括733名无关的受试者。白色样本由来自405个核心家庭的1873名受试者组成。对两个样本中整个LRP5基因的高密度单核苷酸多态性（SNP）进行基因分型并进行分析。结果：连锁不平衡（LD）分析表明，中国人和白人之间的LRP5单倍型结构吻合良好。关联测试表明，在两个样本中，跨5个内含子7到19内含子的LRP5的多态性都与脊柱BMD变化显着相关。特别是，即使在进行多次测试调整后（p = 0.005），中国样本中内含子7中SNP rs491347与脊柱BMD的显着相关性（p = 0.002）也以白色复制。其强烈关联的SNP rs1784235可能导致LRP5中雌激素受体α（ERalpha）结合位点的丢失，这可以部分解释上述复制的关联。但是，我们没有观察到髋部和UD处BMD变化的任何明显复制。在考虑了多次测试后，在这两个站点上主要发现了与BMD变异的关联。性别分层分析进一步表明，中国人和白人中LRP5与BMD的关联分别是由男性和女性引起的。结论：我们的工作支持LRP5基因变异作为人类骨质疏松症和骨折的易感性因素。尤其是，SNP rs491347及其紧密相关的SNP（例如rs1784235）对于人类骨质疏松症的表型可能很重要。

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