LRP5基因多态性与骨密度的关联：一项贝叶斯荟萃分析。

Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

作者信息

Tran Bich N H, Nguyen Nguyen D, Eisman John A, Nguyen Tuan V

机构信息

Bone and Mineral Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia.

出版信息

BMC Med Genet. 2008 Jun 27;9:55. doi: 10.1186/1471-2350-9-55.

BACKGROUND

The low-density lipoprotein receptor-related protein 5 gene (LRP5) was identified to be linked to the variation in BMD in high bone mass pedigrees. Subsequent population-based studies of the association between the LRP5 gene and BMD have yielded conflicting results. The present study was aimed at examining the association between LRP5 gene and BMD by using meta-analysis.

METHODS

A systematic electronic search of literature was conducted to identify all published studies in English on the association between LRP5 gene and osteoporosis-related phenotypes, including bone mineral density and fracture. BMD data were summarized from individual studies by LRP5 genotype, and a synthesis of data was performed with random-effects meta-analyses. After excluding studies on animal and review papers, there were 19 studies for the synthesis. Among these studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD values.

RESULTS

The 10 eligible studies comprised 16,705 individuals, with the majority being women (n = 8444), aged between 18 - 81 years. The overall distribution of genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype frequency varied significantly within as well as between ethnic populations. On random-effects meta-analysis, lumbar spine BMD among individuals with the AA genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023) g/cm2 higher than those with either AV or VV genotype. Similarly, femoral neck BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm2 higher than those without the genotype. While there was no significant heterogeneity in the association between the A1330V polymorphism and lumbar spine BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p = 0.05). The probability that the difference is greater than one standard deviation was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD.

CONCLUSION

These results suggest that there is a modest effect of the A1330V polymorphism on BMD in the general population, and that the modest association may limit its clinical use.

背景

低密度脂蛋白受体相关蛋白5基因（LRP5）被确定与高骨量家系中骨密度的变异有关。随后基于人群的LRP5基因与骨密度之间关联的研究得出了相互矛盾的结果。本研究旨在通过荟萃分析来检验LRP5基因与骨密度之间的关联。

方法

进行了系统的电子文献检索，以识别所有已发表的关于LRP5基因与骨质疏松相关表型（包括骨矿物质密度和骨折）之间关联的英文研究。骨密度数据按LRP5基因型从各个研究中进行汇总，并采用随机效应荟萃分析进行数据合成。在排除动物研究和综述论文后，有19项研究用于合成分析。在这些研究中，10项研究使用了rs3736228（A1330V）多态性并报告了骨密度值。

结果

这10项符合条件的研究共纳入16,705名个体，其中大多数为女性（n = 8444），年龄在18至81岁之间。基因型频率的总体分布为：AA占68%，AV和VV占32%。然而，基因型频率在不同种族人群内部以及之间均存在显著差异。通过随机效应荟萃分析，AA基因型个体的腰椎骨密度平均比AV或VV基因型个体高0.018（95%置信区间[CI]：0.012至0.023）g/cm²。同样，AA基因型携带者的股骨颈骨密度比非该基因型者高0.011（95%CI：0.004至0.017）g/cm²。虽然A1330V多态性与腰椎骨密度之间的关联无显著异质性（p = 0.55），但与股骨颈骨密度的关联存在异质性（p = 0.05）。股骨颈骨密度差异大于一个标准差的概率为0.34，腰椎骨密度为0.54。