Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine
Nucleotide pyrophosphatase gene polymorphism associated with ossification of the posterior longitudinal ligament of the spine
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DOI：
10.1359/jbmr.2002.17.1.138
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发表时间：
2002-01-01
影响因子：
6.2
通讯作者：
Ikegawa, S
中科院分区：
文献类型：
--
作者：
Koshizuka, Y;Kawaguchi, H;Ikegawa, S
脊柱后纵韧带骨化（OPLL）是一种通过压迫脊髓而导致瘫痪的疾病。基于核苷酸焦磷酸酶（Npps）基因与OPLL模型小鼠ttw的异位骨化有关的事实，探讨了人Npps基因是否与OPLL的易感性和严重性相关。首先，我们使用选定的25名年轻发病（< 35岁）或严重骨化（> 10个骨化椎骨）的OPLL患者筛选人类NPPS基因座中的单核苷酸多态性（SNP），并在该基因座中鉴定出三种新的SNP。一项在180例OPLL患者和265例非OPLL对照之间进行的病例对照关联研究显示，这些SNP之一，IVS 15 - 14 T--> C替代，在OPLL患者中更常见（p = 0.022），尤其是在严重骨化（p < 0.0001）和年轻发病（p = 0.002）的患者中。OPLL患者骨化椎体数量的分层研究显示，IVS 15 - 14 T--> C替代（p = 0.013）以及年轻发病（p = 0.046）和女性性别（p = 0.006）与严重骨化相关。我们的结论是，人类NPPS基因中的IVS 15 - 14 T--> C取代不仅与OPLL的易感性有关，而且与OPLL的严重性有关。
Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease that causes paralysis by compressing the spinal cord. Based on the fact that the nucleotide pyrophosphatase (Npps) gene is responsible for ectopic ossification in ttw, an OPLL model mouse, the possibility was explored whether the human NPPS gene is associated with susceptibility to and severity of OPLL. First, we screened for single-nucleotide polymorphisms (SNPs) in the human NPPS locus using selected 25 OPLL patients with young onset (< 35 years old) or severe ossification (> 10 ossified vertebrae), and identified three novel SNPs in the locus. A case-control association study between 180 OPLL patients and 265 non-OPLL controls showed that one of these SNPs, IVS15-14T --> C substitution, was more frequently observed in OPLL patients (p = 0.022), especially in those with severe ossification (p < 0.0001) and young onset (p = 0.002), than in controls. A stratified study with the number of ossified vertebrae in OPLL patients revealed that IVS15-14T --> C substitution (p = 0.013) as well as young onset (p = 0.046) and female sex (p = 0.006) were associated with severe ossification. We conclude that the IVS15-14T --> C substitution in the human NPPS gene is associated not only with susceptibility to, but also with severity of OPLL.