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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470301/
• 关键词: OPLL; ectopic bone formation; linkage study; association study; susceptibility; haplotype analysis; cDNA microarray; 罹患同胞対連鎖解析,; 感受性遺伝子; ゲノム全域; 罹患同胞対連鎖解析

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.

脊柱韧带的骨化（OPLL）是日本骨髓病的主要原因。与内含子6多态性一起观察到与非OPLL的强烈等位基因相关（ - 4）a），其中内含子6（-4a）等位基因在非opll受试者中比OPLL患者更自由，在Col11a2 aximum的可能性计划中鉴定出五个不同的SNP。观察到最常观察到的单倍型的Col11a2单倍型的性别对照和性别特异性。 Col11a2可能参与了广泛的候选基因方法。在最新的在线信息中，我们与126个Opll-sib-pairs进行了非参数链接，以识别负责OPLL的遗传基因座。

项目成果

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）。

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

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,.

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)

Koga, H: "Genetic mapping of ossification of the posterior longitudinal ligament of the spine."Am.J.Hum.Genet.. 62. 1460-1467 (1998)

Koga, H：“脊柱后纵韧带骨化的基因图谱。”Am.J.Hum.Genet.. 62. 1460-1467 (1998)