Internal Medicine, URFOA, IMIM, RETICEF, Hospital del Mar, Autonomous University of Barcelona, Barcelona, Spain.
Osteoporos Int. 2010 Feb;21(2):287-96. doi: 10.1007/s00198-009-0956-4. Epub 2009 May 13.
Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture.
Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures.
Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels.
Upon adjustment for multiple testing (p < 0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p = 0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype "AC" (of SNPs #18 and #17) with FN BMD (p = 0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p < 0.05, belonged to a frequent long-range haplotype.
In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.
骨保护素（Osteoprotegerin，OPG）在骨重塑中发挥关键作用。我们研究了 OPG 基因上 24 个多态性和单倍型与骨密度和骨折之间的关联。在多重检验校正后，一个 SNP 和两个块单倍型与 FN 骨密度显著相关。另外两个块单倍型与骨折相关。
骨保护素（Osteoprotegerin，OPG）在骨重塑中发挥关键作用。在此，我们研究了 OPG 基因上的多态性和单倍型与骨矿物质密度（Bone mineral density，BMD）和骨折之间的关系。
选择了 24 个单核苷酸多态性（Single nucleotide polymorphisms，SNPs）来覆盖六个单倍型块，并对 964 名绝经后西班牙女性进行了基因分型。使用 HaploStats 建立单倍型。通过 GLM（用于 BMD）和逻辑回归（用于骨折）在单 SNP 和单倍型水平上分析关联。
在进行多重检验校正（p < 0.0073）后，一个 SNP（SNP #17，rs1032129）仍然与 FN 骨密度显著相关（p = 0.001）。四个块单倍型通过了多重检验校正。其中两个与 FN 骨密度相关，两个与骨折相关。SNP #18 和 #17 的单倍型“AC”与 FN 骨密度的相关性（p = 0.0002）比 SNP#17 单独的相关性更强，并且是整体最佳结果。对结果的全面评估表明，所有具有保护作用的等位基因和单倍型（p < 0.05）都属于一种常见的长程单倍型。
总之，这些结果提供了一个详细的 OPG 基因常见变异和单倍型在骨表型中作用的图。
