Liu Wenjun, Sun Guisen, Guo Longsheng, Wang Lulu, Fan Weiqiang, Lang Minglei, Chen Dan, Yi Xinhao
Department of Orthopedic Surgery, Shengli Oilfield Central Hospital, Dongying, People's Republic of China.
J Genet. 2017 Dec;96(6):867-872. doi: 10.1007/s12041-017-0874-8.
This study aimed to explore whether the genetic variant of COL11A1 is functionally associated with the development of lumbar disc herniation (LDH) in Chinese population. SNP rs1676486 of COL11A1 was genotyped in 647 patients and 532 healthy controls. The differences of genotype and allele distributions between LDH patients and healthy controls were evaluated using the χ² test. One-way ANOVA test was used to compare the relationship between genotypes and clinical features including tissue expression of COL11A1 and the degree of disc degeneration. Patients were found to have a significantly higher frequency of TT than the controls (10.2% versus 7.3%, P = 0.004). Besides, the frequency of allele T was found to be remarkably higher in the patients than the controls (34.8% versus 28.1%, P < 0.001) with an odds ratio of 1.36 (95% confidential interval=1.14-1.63). Patients with genotype TT were found to have remarkably more severe disc degeneration (P = 0.02). Besides, the expression of COL11A1 in the lumbar disc was significantly lower in the patients with genotype TT than in those with genotype CT or CC (P < 0.001). Moreover, the expression level was inversely correlated with the severity of disc degeneration (P < 0.001). We confirmed that the rs1676486 of COL11A may be functionally associated with LDH in the Chinese population. Extracellular matrix related proteins may play an important role in the pathogenesis of LDH. Our findings shed light on a better understanding of the pathogenesis of LDH, which could be a promising target for a novel treatment modality of LDH.
本研究旨在探讨在中国人群中，COL11A1基因变异是否与腰椎间盘突出症（LDH）的发生存在功能关联。对647例患者和532例健康对照者进行了COL11A1基因的单核苷酸多态性（SNP）rs1676486基因分型。采用χ²检验评估LDH患者与健康对照者之间基因型和等位基因分布的差异。使用单因素方差分析来比较基因型与临床特征之间的关系，这些临床特征包括COL11A1的组织表达以及椎间盘退变程度。结果发现，患者中TT基因型的频率显著高于对照组（10.2%对7.3%，P = 0.004）。此外，发现患者中等位基因T的频率显著高于对照组（34.8%对28.1%，P < 0.001），优势比为1.36（95%置信区间 = 1.14 - 1.63）。发现基因型为TT的患者椎间盘退变明显更严重（P = 0.02）。此外，基因型为TT的患者腰椎间盘COL11A1的表达明显低于基因型为CT或CC的患者（P < 0.001）。而且，表达水平与椎间盘退变的严重程度呈负相关（P < 0.001）。我们证实，COL11A的rs1676486在中国人群中可能与LDH存在功能关联。细胞外基质相关蛋白可能在LDH的发病机制中起重要作用。我们的研究结果有助于更好地理解LDH的发病机制，这可能是LDH新型治疗方式的一个有前景的靶点。
