椎间盘稳定性相关基因与环境危险因素的交互作用模式对广西壮族人群腰椎间盘突出症易感性的影响

Lumbar disc herniation (LDH) is one of the most common spinal disorders. Approximately 20% of people have experienced low back pain owing to LDH at some point in their life. LDH can lead to diminished function, loss of productivity, loss of work, psychological distress, and increased health care costs. As such, LDH poses considerable financial burden to nations through the direct cost of LDH treatments and the indirect cost due to loss of working productivity. Although LDH is a prevailing disorder, the factors that contribute to LDH are still not fully understood. A variety of environmental factors, such as occupation, biopsychological factors, smoking, and obesity, have been suggested to be associated with LDH. Recently, the role of genetic factors of LDH has been shown in several studies. Furthermore, these genetic studies have mainly focused on candidate genes associated with intervertebral disc stability. The objective of the present study is three-fold: (1) to determine whether single nucleotide polymorphisms in susceptibility genes including ASPN, COL11A1, GDF-5, MMP-9, SKT and THBS-2 might play some role in LDH; (2) to determine the environmental factors associated with LDH; (3) to analysis the susceptibility of LDH in Guangxi Zhuang population by genetic-environmental interaction mode.

腰椎间盘突出症（lumbar disc herniation，LDH）是脊柱外科常见疾病之一，约1/5的腰腿痛患者是由腰椎间盘突出症造成，给家庭及社会造成巨大的经济负担。流行病学调查发现环境因素是引起椎间盘退变导致腰椎间盘突出症的主要危险因素。近年来，越来越多的研究证实遗传因素与腰椎间盘突出症的发病密切相关。国外学者的初步研究表明椎间盘稳定性相关基因在腰椎间盘突出症的发病过程中发挥着重要作用，并提示腰椎间盘突出症可能与这些已知的基因异常相关，并为进一步研究提供了候选位点和易感基因。本课题旨在明确ASPN、COL11A1、GDF-5、MMP-9、SKT、THBS-2等椎间盘稳定性相关基因，以及性别、年龄、体重、职业、腰椎外伤史、少数民族生活方式等因素与广西壮族人群腰椎间盘突出症易感性之间的关系，并构建环境危险因素与遗传因素之间的交互作用模式以进一步分析其对腰椎间盘突出症患者的影响。

腰椎间盘突出症是骨骼肌肉系统最常见的退变性疾病之一。有研究表明椎间盘稳定性相关基因在腰椎间盘突出症的发病过程中发挥着重要作用，并为进一步研究提供了候选基因和易感位点。本课题在既往研究的基础上，采用病例-对照研究方法，对COL11A1、ADAMTS5、ADAMTS4、MMP9、MMP13、ASPN、GDF5、SKT、THBS2 等椎间盘稳定性相关基因位点进行筛查，发现COL11A1基因（rs1337185位点）和ADAMTS5基因（rs162509位点）与广西壮族和汉族人群腰椎间盘突出症易感性存在显著相关性，rs1337185位点的C等位基因携带者和rs162509位点的G等位基因携带者的腰椎间盘突出症发病风险明显增高，为进一步研究腰椎间盘突出症的相关发病机理提供坚实的理论依据。