Does the collagen IX tryptophan polymorphism trigger lumbar disc degeneration?

我们分析了将色氨酸残基引入分子的三螺旋区域的IX型胶原基因多态与腰椎间盘退变的关系。在日本健康对照组中，该多态的等位基因频率为21%(Clin Rheumatol)。我们证明该基因多态与腰椎滑脱症相关(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(手稿正在准备中)中，该基因多态与严重的腰椎间盘退变显著相关，这一点通过MRI得到了证实。从患者取出的椎间盘组织的蛋白质分析显示，IX型胶原含量很低(手稿正在准备中)，表明该分子的破坏参与了早发性间盘基质退变的发展。最后，我们确认了一个由IX型胶原基因突变引起的日本多发性骨盆发育不良家系(Clin Rheumatol在新闻中)，显示可能有腰椎滑脱症的易感性(手稿正在准备中)。综上所述，我们的结果暗示IX型胶原的基因变异是日本人群腰椎间盘退变的一个危险因素。

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.