Does the collagen IX tryptophan polymorphism trigger lumbar disc degeneration?

我们分析了IX型胶原基因多态性与腰椎间盘退变的关系，该基因多态性在日本健康对照中的等位基因频率为21%（Clin Rheumatol出版）。我们证明了多态性与腰椎滑脱相关（J Bone Joint Surg Br 2004）。我们还发现，在年轻一代的日本腰椎间盘突出症患者中，该多态性与MRI证实的严重椎间盘退变显著相关（手稿正在准备中）。从患者中取出的椎间盘组织的蛋白质分析显示，IX型胶原蛋白含量非常低（手稿在准备中），表明这种分子的破坏与早发性椎间盘基质变性的发展有关。最后，我们确定了一个日本家族，其多发性骨骺发育不良是由IX型胶原基因突变引起的（Clin Rheumatol in press），显示了腰椎滑脱的可能易感性（手稿正在准备中）。总之，我们的研究结果表明，IX型胶原基因变异是日本人群腰椎间盘退变的危险因素。

We analyzed the type IX collagen gene polymorphism, which introduces tryptophan residue into the triple helical region of the molecule, in relation with lumbar disc degeneration.The allele frequency of the polymorphism was 21% among the Japanese healthy controls (Clin Rheumatol in press). We demonstrated that the polymorphism was associated with lumbar spondylolisthesis (J Bone Joint Surg Br 2004). We also found that the polymorphism was significantly related to severe disc degeneration, evidenced by MRI, among the young generation of the Japanese patients with lumbar disc herniation (manuscript in preparation). Protein analysis of the removed disc tissues from the patients revealed that the type IX collagen content was very low (manuscript in preparation), indicating that the destruction of this molecule is involved in the development of early-onset disc matrix degeneration. Lastly, we identified a Japanese family with multiple epiphyseal dysplasia caused by the type IX collagen gene mutation (Clin Rheumatol in press), showing a possible predisposition to lumbar spondylolisthesis (manuscript in preparation).In summary, our results imply that the genetic variation of collagen IX is a risk factor for lumbar disc degeneration in the Japanese population.