Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Background
A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.
Methods
Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.
Results
A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm2, 95% CI = 0.01-0.03, P < 10-4; at femur neck (FN): WMD = 0.01g/cm2, 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm2, 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm2, 95% CI = 0.02-0.03, P < 10-5; WMD at FN = 0.01g/cm2, 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm2, 95% CI = 0.01-0.05, P = 0.005).
Conclusion
This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.

研究背景
已有多项研究探讨了低密度脂蛋白受体相关蛋白5基因（low-density lipoprotein receptor-related protein 5 gene, LRP5）的多态性与相关表型的关联，但既往研究结果尚无定论。为此，本研究针对LRP5基因多态性与骨密度（bone mineral density, BMD）的关联开展荟萃分析，以评估其合并效应量。

研究方法
检索PubMed、EMBASE及ISI Web of Science数据库中已发表的符合纳入标准的文献，采用固定效应模型或随机效应模型计算加权均数差（weighted mean difference, WMD）与95%置信区间（confidence interval, CI）。

研究结果
本荟萃分析共纳入19项研究，涉及25773名研究对象。其中17项研究探讨了A1330V多态性与骨密度的关联，8项聚焦于V667M多态性，另有2项分析了Q89R多态性。携带A1330V位点AA基因型的研究对象，其骨密度显著高于AV/VV基因型携带者[腰椎（lumbar spine, LS）：WMD=0.02g/cm²，95%CI=0.01~0.03，P<10^-4；股骨颈（femur neck, FN）：WMD=0.01g/cm²，95%CI=0.00~0.02，P=0.01]或VV基因型携带者[腰椎（LS）：WMD=0.02g/cm²，95%CI=0.01~0.04，P=0.01]。针对V667M位点的分析同样检出显著关联（VV基因型对比VM/MM基因型：腰椎WMD=0.02g/cm²，95%CI=0.02~0.03，P<10^-5；股骨颈WMD=0.01g/cm²，95%CI=0.01~0.02，P=0.0002）。就Q89R位点而言，携带QQ基因型的研究对象在股骨颈部位的骨密度显著高于QR/RR基因型携带者（WMD=0.03g/cm²，95%CI=0.01~0.05，P=0.005）。

研究结论
本荟萃分析结果显示，LRP5基因多态性可能与腰椎及股骨颈的骨密度存在轻度关联。