A functional polymorphism in COL11A1, which encodes the α1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation
A functional polymorphism in COL11A1, which encodes the α1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation
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DOI：
10.1086/522377
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发表时间：
2007-12-01
影响因子：
9.8
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Mio, Futoshi;Chiba, Kazuhiro;Ikegawa, Shiro
腰椎间盘突出症是腰椎间盘髓核的退变和突出，是最常见的肌肉骨骼疾病之一。然而，其病因和发病机制仍不清楚。XI型胶原蛋白对于软骨胶原蛋白形成和细胞外基质的组织化是重要的。我们确定了日本人群中XI型胶原基因之一COL 11 A1和LDH之间的关联。编码XI型胶原α 1链的COL 11 A1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程度呈负相关。单核苷酸多态性（c.4603C -> T [rs 1676486]）与LDH的相关性最显著（P = 3.3 x 10（-6）），含有疾病相关等位基因的转录本由于其稳定性降低而减少。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。
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.