Genetic studies of ossification of the posterior longitudinal ligament of the spine

脊柱后纵韧带骨化的遗传学研究

基本信息

批准号：
10470301
负责人：
INOUE Ituro
金额：
$ 8.19万
依托单位：
The University of Tokyo (2000)Gunma University (1998-1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

Ossification of the posterior longitudinal ligament of the spine(OPLL)is the leading cause of myelopathy in Japan. In earlier studies, we provided genetic linkage and allelic association evidence of distinct differences in the human collagen α2(XI)gene(COL11A2)that might constitute inherited predisposition to OPLL.A strong allelic association with non-OPLL(P=0.0003)was observed with an intron 6 polymorphism(Intron 6(-4A)), where the intron 6(-4A)allele is more frequently observed in non-OPLL subjects than in OPLL patients. In addition, five distinct SNPs, identified in COL11A2, were combined to construct possible haplotypes by use of a maximum likelihood program. Estimated haplotype frequency was compared between OPLL patients and non-OPLL controls and gender-specific association of COL11A2 haplotype with OPLL was observed. The most commonly observed haplotype was significantly increased in male patients(p=0.0003)but not in female patients(p=0.21). OPLL is a complex disease, and several genetic factors other COL11A2 are probably involved in the etiology, so the more extensive candidate gene approach was performed. We selected a total of 88 candidate genes based on two separate investigations. 24 genes differentially regulated during osteoblastic differentiation were selected by cDNA microarray analysis, and subjected to linkage analysis. We also selected 64 candidate genes that are possibly involved in bone metabolism or related conditions. Microsatellite markers, locating close to or within the candidate genes were obtained in the latest online information. With these markers we performed non-parametric linkage study with 126 OPLL sib-pairs to identify genetic loci responsible in OPLL.

脊柱后纵韧带的骨化（OPLL）是日本骨髓病的主要原因。在较早的研究中，我们提供了人类胶原蛋白α2（XI）基因（COL11A2）在遗传联系和等位基因关联证据中，可能构成可能遗传的OPLL的易于遗传的倾向。非opll（p = 0.0003）的强烈等位基因相关（p = 0.0003）均与Intron 6 Polymorprism（Intron 6（Introne）6（-4a）6（-4a）观察到更多的等位基因（p = 0.0003）。非OPLL受试者比OPLL患者。此外，将五个不同的SNP（在Col11a2中鉴定出来，通过使用最大似然程序构建可能的单倍型。比较了OPLL患者和非OPLL对照组之间的估计单倍型频率以及Col11a2单倍型与OPLL的性别特异性关联。最常见的单倍型OPLL是一种复杂的疾病，其他COL11A2的遗传因素可能参与病因，因此进行了更广泛的候选基因方法。我们基于两项单独的研究选择了总共88个候选基因。通过cDNA微阵列分析选择了在成骨细胞分化过程中对差异调节的24个基因，并进行连锁分析。我们还选择了64个可能参与骨代谢或相关疾病的候选基因。在最新的在线信息中获得了靠近候选基因或候选基因内或内部的微卫星标记。使用这些标记，我们通过126个OPLL SIB对进行了非参数连锁研究，以识别负责OPLL负责的遗传基因座。

项目成果

期刊论文数量（54）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nakajima, T., Tong, C., Rohrwasser, A., Bloem, LJ., Pratt, JH., Inoue, I., Lalouel, J-M.: "Functional analysis of a mutation occurring between the two in-frame AUG codons of human angiotensinogen."J.Biol.Chem.. 274. 35749-35755 (1999)

Nakajima, T.、Tong, C.、Rohrwasser, A.、Bloem, LJ.、Pratt, JH.、Inoue, I.、Lalouel, J-M.：“两个框内 AUG 密码子之间发生的突变的功能分析

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

前田真吾: "後縦靭帯骨化症候補遺伝子COL11A2の多型によるmRNA発現の差"脊椎外科. (in press). (2000)

Shingo Maeda：“由于后纵韧带骨化候选基因 COL11A2 的多态性而导致的 mRNA 表达差异”，脊柱外科（2000 年出版）。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Maeda,S: "Gender-specific haplotype association of collagen α2 (Xl) gene in ossification of the posterior longitudinal ligament of the spine."J.Hum.Genet.. 46,. 1-4 (2001)

Maeda,S：“脊柱后纵韧带骨化中胶原蛋白 α2 (Xl) 基因的性别特异性单倍型关联。”J.Hum.Genet.. 46,.

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Maeda, S., Koga, H., Matsunaga, S., Numasawa, T., Takeda, J., Harata, S., Sakou, T., Inoue, I.: "Gender-specific haplotype association of collagen α2(XI)gene in ossification of the posterior longitudinal ligament of the spine."J.Hum.Genet.. 46. 1-4 (2001)

Maeda, S.、Koga, H.、Matsunaga, S.、Numasawa, T.、Takeda, J.、Harata, S.、Sakou, T.、Inoue, I.：“胶原蛋白 α2 的性别特异性单倍型关联（ XI)脊柱后纵韧带骨化的基因。“J.Hum.Genet..46.1-4(2001)