椎间盘退变的相关遗传易感基因研究进展

Research progress of genetic susceptibility genes associated with intervertebral disc degeneration

椎间盘退变为多因素造成的慢性病变过程，其可致椎间盘结构、功能发生改变。目前，其病理生理过程仍未彻底清楚，但近年来相关研究报告越来越多地显示，除环境影响外，一些基因的多态性同样可导致椎间盘退变发病风险的增高，故综述并探讨椎间盘退变存在的相关基因因素及其在退变的病理生理过程中普遍作用，阐明与疾病相关的基因组分可对病变进展机制有更深入的了解，并对临床患者的早期诊断、早期预防有重要意义。通过查阅近年来的相关文献，选取15个目前普遍认可的基因，对其进行多态性、疾病关联性总结，以深入了解各个基因所发挥的功能性作用。具体阐述了如下基因：蛋白聚糖、Ⅰ型、Ⅸ型、Ⅺ型胶原（collagenTypesⅠ，Ⅸ，Ⅺ）、纤连蛋白、透明质酸与蛋白多糖连接蛋白（ hyaluronan and proteoglycan link protein, HAPLN）1、软骨中间层蛋白（cartilage intermediate layer protein, CILP）、基质金属蛋白酶（matrix metalloproteinase, MMP）、2、3、帕金森一泛素蛋白连接酶（Parkinson protein 2 E3 ubiquitin protein ligase, PARK2）、白细胞介素（interleukin，IL）1、6、维生素D受体（vitaminDreceptor，VDR），各基因均参与编码椎间盘退变过程中的相关功能蛋白。其中，蛋白聚糖，Ⅸ型胶原，MMP-3，IL-1、6，VDR的多态性变化显示其与病变过程相关性较高。基因研究对于退变机制的理解十分必要，基因信息未来也可能充当决定个体患病风险的预测模型。

The process of intervertebral disc degeneration, which could resuh in intervertebral disc structural and func- tional change, is a chronic one with multiple factors. The pathophysiologic process is still not completely find out. More and more research reports manifest that certain gene polymorphism also lead to increased risk of intervertebral disc degeneration except en- vironmental factors. Discussions about related genetic factors and their pathophysiological role in the process of degeneration could have a further understanding to disease development. Elucidating genetic components which are associated with degenera- tion could not only provide insights into the mechanism of the process, but also have clinical significance for early diagnosis and prevention. In order to have a thorough understanding of functional role played by different genes, this paper summarize polymor- phism and disease correlation by selecting 15 genes after reviewed the related literature published in recent years. Genetic poly- mo133hisms in 15 genes have been analyzed in association with intervertebral disc degeneration, including aggrecan, collagen Types Ⅰ , Ⅸ and Ⅺ, fibronectin, HAPLN 1, CILP, MMP-1, 2 and 3, PARK2, IL-1, 6 and VDR. Each genetic polymorphism codes for a protein which has a functional role in the pathogenesis of disease. Among the 15 genes analyzed, polymorphisms in aggrecan, Type Ⅸ collagen, MMP3, IL1, IL6 and VDR show the most promise as functional variants. Genetic studies are necessary for understand- ing the mechanism of the degeneration. Relevant genetic information could be used as a predictive model for determining individu- als＇ risk for intervertebral disc degeneration eventually.