Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine
Large-scale screening for candidate genes of ossification of the posterior longitudinal ligament of the spine
复制标题
DOI：
10.1359/jbmr.2002.17.1.128
复制
发表时间：
2002-01-01
影响因子：
6.2
通讯作者：
Inoue, I
中科院分区：
文献类型：
--
作者：
Furushima, K;Shimo-Onoda, K;Inoue, I
脊柱后纵韧带骨化（OPLL）是日本人的主要脊髓病，在日本人和其他亚洲人中通常通过椎旁韧带异位骨形成来诊断。为了检测与OPLL相关的遗传决定因素，我们进行了广泛的非参数连锁研究与126个受影响的同胞对使用不同的分析，SIBPAL和GENEHUNTER的各种候选基因的标记。88个候选基因的选择，通过比较基因的互补DNA（cDNA）微阵列分析系统的基因表达谱在成骨分化的人骨髓间充质干细胞与已知的基因参与骨代谢。在成骨细胞分化过程中调控的24个基因中，只有一个α B晶体基因显示出连锁的证据（p = 0.016，非参数连锁[NPL]评分= 1.83）。在已知与骨代谢相关的64个基因中，通过SIBPAL分析，7个显示出弱的连锁证据（p < 0.05）：钙粘蛋白13（CDH13）、骨形态发生蛋白4（BMP 4）、蛋白聚糖1（PRG 1）、转化生长因子β 3（TGF β 3）、骨桥蛋白（OPN）、甲状旁腺激素受体1（PTHR 1）和胰岛素样生长因子1（IGF 1）。在这些基因中，BMP 4（NPL = 2.23）、CDH13（NPL = 2.00）、TGFb3（NPL = 1.30）、OPN（NPL = 1.15）和PTHR 1（NPL = 1.00）通过GENEHUNTER显示出连锁的证据。只有BMP 4达到了提示性证据的标准。由于该基因是一个众所周知的成骨功能的因素，BMP 4的多态性应在进一步的研究中进行筛选。
Ossification of the posterior longitudinal ligament of the spine (OPLL) is the predominant myelopathy among Japanese, and is usually diagnosed by ectopic bone formation in the paravertebral ligament in Japanese and other Asians. To detect genetic determinants associated with OPLL, we performed an extensive nonparametric linkage study with 126 affected sib-pairs using markers for various candidate genes by distinct analyses, SIBPAL and GENEHUNTER. Eighty-eight candidate genes were selected by comparing the genes identified by complementary DNA (cDNA) microarray analysis of systematic gene expression profiles during osteoblastic differentiation of human mesenchymal stem cells with the genes known to be involved in bone metabolism. Of the 24 genes regulated during osteoblastic differentiation, only one, the alpha B crystalline gene, showed evidence of linkage (p = 0.016, nonparametric linkage [NPL] score = 1.83). Of 64 genes known to be associated with bone metabolism, 7 showed weak evidence of linkage by SIBPAL analysis (p < 0.05): cadherin 13 (CDH13), bone morphogenetic protein 4 (BMP4), proteoglycan 1 (PRG1), transforming growth factor beta 3 (TGFb3), osteopontin (OPN), parathyroid hormone receptor 1 (PTHR1), and insulin-like growth factor 1 (IGF1). Among these genes, BMP4 (NPL = 2.23), CDH13 (NPL = 2.00), TGFb3 (NPL = 1.30), OPN (NPL = 1.15), and PTHR1 (NPL = 1.00) showed evidence of linkage by GENEHUNTER. Only BMP4 reached criteria of suggestive evidence of linkage. Because this gene is a well-known factor in osteogenetic function, BMP4 should be screened in further study for the polymorphism responsible.