Osteoarthritis Susceptibility Genes Influence the Association Between Hip Morphology and Osteoarthritis
Osteoarthritis Susceptibility Genes Influence the Association Between Hip Morphology and Osteoarthritis
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DOI：
10.1002/art.30288
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发表时间：
2011-05-01
影响因子：
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通讯作者：
Meulenbelt, I.
中科院分区：
文献类型：
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作者：
Waarsing, J. H.;Kloppenburg, M.;Meulenbelt, I.
客观的。已确定的骨关节炎（OA）易感基因主要活跃于骨骼发育，因此可能影响关节几何形状。由于非最佳关节几何形状是发生 OA 的危险因素，因此我们研究了这些基因是否以及如何影响从非最佳关节几何形状导致髋部 OA 的路径。方法。遗传学、骨关节炎和进展研究中的受试者（由多个关节部位患有骨关节炎症状的兄弟姐妹组成）的臀部形状是通过将统计形状模型应用于放射照片来量化的。形状方面（模式）与 OA 特征相关。然后我们测试了形状模式与 GDF5、FRZB 和 DIO2 的 OA 易感性单核苷酸多态性 (SNP) 的关联。结果。 23 种形状模式中的 4 种（模式 1、模式 17、模式 18 和模式 21）与 OA 特征密切相关。我们观察到 DIO2 rs12885300 携带者状态与模式 1 的髋关节 OA 特征之间存在显着的交互作用 (P = 0.005)。这表明髋部形状的这一特定方面仅在易感性等位基因携带者中与 OA 特征相关。结论。我们的结果表明，DIO2 的 rs12885300 SNP 更有可能增加软骨对非最佳骨形状的脆弱性，而不是直接影响这些形状的形成。
Objective. The identified osteoarthritis (OA) susceptibility genes are mainly active in skeletal development and could thus affect joint geometry. Because nonoptimal joint geometry is a risk factor for the development of OA, we investigated if and how the path that leads from nonoptimal joint geometry to OA of the hip is influenced by these genes.Methods. The shape of the hips of subjects in the Genetics, Osteoarthritis and Progression Study, consisting of sibling pairs with symptomatic OA at multiple joint locations, was quantified by applying a statistical shape model to radiographs. Shape aspects (modes) were correlated to OA characteristics. We then tested for the association of shape modes with OA susceptibility single-nucleotide polymorphisms (SNPs) of GDF5, FRZB, and DIO2.Results. Four of 23 shape modes (mode 1, mode 17, mode 18, and mode 21) were strongly associated with OA characteristics. We observed a significant interaction between carrier status of DIO2 rs12885300 and hip OA characteristics for mode 1 (P = 0.005). This indicates that this specific aspect of hip shape correlates with OA characteristics only in carriers of the susceptibility allele.Conclusion. Our results suggest that it is more likely that the rs12885300 SNP of DIO2 increases the vulnerability of cartilage to nonoptimal bone shapes rather than directly influencing the formation of these shapes.