Mio Futoshi, Chiba Kazuhiro, Hirose Yuichiro, Kawaguchi Yoshiharu, Mikami Yasuo, Oya Takeshi, Mori Masaki, Kamata Michihiro, Matsumoto Morio, Ozaki Kouichi, Tanaka Toshihiro, Takahashi Atsushi, Kubo Toshikazu, Kimura Tomoatsu, Toyama Yoshiaki, Ikegawa Shiro
Laboratory for Bone and Joint Diseases, School of Medicine, Keio University, Tokyo.
Am J Hum Genet. 2007 Dec;81(6):1271-7. doi: 10.1086/522377. Epub 2007 Oct 16.
Lumbar disc herniation (LDH), degeneration and herniation of the nucleus pulposus of the intervertebral disc (IVD) of the lumbar spine, is one of the most common musculoskeletal diseases. Its etiology and pathogenesis, however, remain unclear. Type XI collagen is important for cartilage collagen formation and for organization of the extracellular matrix. We identified an association between one of the type XI collagen genes, COL11A1, and LDH in Japanese populations. COL11A1, which encodes the alpha 1 chain of type XI collagen, was highly expressed in IVD, but its expression was decreased in the IVD of patients with LDH. The expression level was inversely correlated with the severity of disc degeneration. A single-nucleotide polymorphism (c.4603C-->T [rs1676486]) had the most significant association with LDH (P=3.3 x 10(-6)), and the transcript containing the disease-associated allele was decreased because of its decreased stability. These observations indicate that type XI collagen is critical for IVD metabolism and that its decrease is related to LDH.
腰椎间盘突出症（LDH）是腰椎椎间盘（IVD）髓核退变和突出所致，是最常见的肌肉骨骼疾病之一。然而，其病因和发病机制尚不清楚。XI型胶原蛋白对于软骨胶原蛋白的形成以及细胞外基质的组织非常重要。我们在日本人群中发现XI型胶原蛋白基因之一COL11A1与LDH之间存在关联。编码XI型胶原蛋白α1链的COL11A1在IVD中高表达，但在LDH患者的IVD中其表达降低。表达水平与椎间盘退变的严重程度呈负相关。单核苷酸多态性（c.4603C→T [rs1676486]）与LDH的关联最为显著（P = 3.3×10^(-6)），并且含有疾病相关等位基因的转录本由于稳定性降低而减少。这些观察结果表明，XI型胶原蛋白对IVD代谢至关重要，其减少与LDH有关。
