脊髓型颈椎病危险因素、证候类型以及单核苷酸多态性关系的研究

Abstract: Cervical spondylotic myelopathy onsets occult, and the outcome of it is also varied. Before recommend an appropriate treatment, we need to have a knowledge of the CSM. The occurrence and development of cervical spondylotic myelopathy has been confirmed to be closely related to disc degeneration and environmental risk factors, including age, occupation and so on. Disc degeneration is evidenced to have relationship with gene polymorphism of collagen, metal matrix-degrading enzyme. This study is on the basis of "Epidemiological study of China's urban population about cervical spondylosis" to establish cohort study of cervical spinal cord patients (800) and control (1600). Imaging examination would be taken to clear directly pathological changes with CSM, questionnaires such as ASSIST and IPAQ would be taken to screen the environmental risk factors for CSM, High resolution melting curve analysis (HRM) would be taken to explicit risk genes for CSM, and the use of cluster analysis of the syndrome would define the regulation of the CSM syndrome. On this basis, three-year follow-up woul be taken to clear the relationship between direct pathological changes, environmental risk factors, dangerous gene and syndromes to the outcome of CSM. The final purpose is to identify the influencing factors and molecular genetic basis to the occurrence and development of CSM.

脊髓型颈椎病（CSM）起病隐匿，转归各有差异，深入了解脊CSM的病程与证候类型有助于选择合适的治疗方法。CSM与椎间盘退变及年龄、职业、生活习惯等危险因素相关，而椎间盘退变与各型胶原、金属基质降解酶等基因多态性有关。本研究在"中国城市人群颈椎病的流行病学调查研究"基础上，建立脊髓型颈椎病患者（800人）和对照（1600人）队列，通过影像学检查明确CSM发病的病理改变，采用问卷调查，包括酒精、烟草和精神活性物质使用相关问题筛查测试（ASSIST）和国际体力活动问卷(IPAQ)等，明确CSM的环境危险因素，采用高分辨率溶解曲线分析技术(HRM)方法检测筛查危险基因，并通过证素类据进行CSM的证候分析。在此基础上，进行三年随访，明确病理改变、环境危险因素、危险基因与证候对疾病转归的影响，及其中的相关性，从而确定CSM的发生、发展和预后的影响因素和证候的分子遗传学基础。

本课题前期开展脊髓型颈椎病（CSM）患者的病历收集工作，并与上海交通大学Bio-X实验室合作完成了381例CSM患者和383例正常对照人群的血样收集及GWS检测，筛选潜在危险基因6个。通过206例患者的三年随访，筛选出年龄（OR=0.409，P<0.005），与基线JOA（P=0.004，OR=3.519）作为CSM非手术治疗预后判断最主要的因素。采用线性分析制作检测模型，得出预测模型公式为：预期JOA=11.971-0.038×年龄+0.289×基线JOA。项目系统整理出CSM的相关证素及证候，制定“CSM的中医四诊资料采集问卷”，共调查CSM患者101例，通过对调查结果进行统计学分析得到CSM证候分布规律18条；通过聚类分析得出CSM的中医证型总体上可分为心脾两虚，肾阳亏虚及经脉闭阻三大类。CSM转归各有差异，深入了解脊CSM的病程与证候类型有助于选择合适的治疗方法。本研究进行三年随访，明确了病理改变、环境危险因素、危险基因与证候对疾病转归的影响，从而确定CSM的发生、发展和预后的影响因素和证候的分子遗传学基础。