中国南方汉族人群腰椎Modic改变与易感基因相关性的分子流行病学研究

Modic changes, vertebral endplate changes and bone marrow changes visible in magnetic resonance imaging, are closely associated with low back pain and disc degeneration. As Modic changes and disk degeneration are associated with many congenital and environmental factors, it is reasonable to speculate that persons from areas with major transitions might have a higher prevalence of low back pain. The forces of globalization and urbanization, together with the economic reform and social development have been associated with a changing profile in the health risks facing China's population. As people flood to the cities, their lifestyles become increasingly sedentary. A report from World Health Organization showed the picture in China is troubling. Although the precise role or function of Modic changes is not known, they may play a role in intervertebral disc degeneration. Unlike disc degeneration, where enormous research attentions have been placed on investigating biological factors and the interaction between these factors, little has been performed on Modic changes. Therefore, as part of a large scale population-based cohort study of the southern Chinese Han population examining genetic factors for lumbar degeneration, this study aimed to assess the prevalence, potential determinants of Modic changes, and their association with other imaging findings. The purpose of the current work is to examine the role of identified genetic risk factors of low back disorders in Modic changes in a population of southern Chinese Han population and to explore the correlation between the genotypes and phenotypes, genotypes and their environments.

随着我国经济发展和都市化的进程，生活方式的改变而导致人群腰背痛的发生率不断增高。Modic改变即脊柱退变疾病中椎体终板及终板下骨质MRI的信号改变，基因学异常可能是Modic改变发生的基础之一。我们之前进行的大规模中国南方人群腰椎退变的临床流行病学和影像学研究表明Modic改变与腰背痛和腰椎退行性疾病显著相关。为了更好地进行临床干预和生物学修复，明确Modic改变的分子发生机制十分必要。在已获得的中国南方汉族人群腰椎退变的流行病临床影像学研究结果基础上，本研究着重进行腰椎磁共振影像学Modic改变，腰背痛症状，Modic改变发生与性别、年龄、体重、职业、腰椎外伤史等一般资料间的相关性，以及和相关易感基因的相关性。研究旨在发现与Modic改变和腰背痛症状相关的遗传危险因子，研究基因－基因、基因－表型、基因－环境之间的关系，为Modic改变和腰背痛的预防和将来生物学治疗的临床应用提供理论依据。

评估中国南方都市人群中腰椎间盘退行性变化的程度，发生率和在不同椎间节段的分布状况。方法 共有1724例志愿者参加了该研究，其中1062例为女性，662例为男性，年龄范围在18岁至88岁之间，平均年龄为38.04岁。对所有参加者进行了影像学检查，临床体格检查和症状学评分。用1.5 T的磁共振系统进行脊柱扫描腰椎T2矢状位序列成像。在所得MRI图像的基础上，对腰椎间盘退变进行评分。评估每个腰椎节段的Modic改变，许莫氏结节（Schmorl nodes）和高信号区（HIZ）。对Modic改变的患者进行基因测序，分别测8个基因的13个位点（COL9A2, COL9A3, COL11A2, IL1A, IL1B, IL6, MMP3和VDR）。.结果 许莫氏结节的发生与性别相关，许莫氏结节在男性中发生率更高。卡方检验发现，许莫氏结节、Modic改变和高信号区三种影像学表现与腰椎间盘退变的相关性依次增强，均具有统计学意义。高信号区和Modic改变与年龄呈显著相关 ( P＜0.01)。许莫氏结节和高信号区在腰椎中的分布规律为：许莫氏结节从上（头端）至下（尾端）呈降序分布；椎间盘高信号区从上至下呈升序分布。腰椎间盘退变评分（DDD分数）与身体质量指数呈正相关 ( P＜0.01)。DDD评分结果在男女性别间无明显差异。从上（头端）至下（尾端），腰椎间盘节段的退变发生呈持续升高趋势。腰椎间盘退变在男女性别之间有一定程度的差异( P＜0.05)。腰椎间盘退变在年轻人群中总体发生率高，男性为35.3%，女性为33.9%。通过基因学分析，Modic改变发现与白细胞介素1A（IL1A）和MMP3多态性相关。结论 许莫氏结节的发生与年龄无关，其分布在男女性别之间有明显差异。研究发现腰椎间盘退变在中国南方人群中呈高发状态，特别是年轻成人中常见。身体质量指数与腰椎间盘退变显著相关。25-35岁年龄段的男性比女性更易患腰椎间盘退变，我们推测是外界环境因素所致。本研究发现了Modic改变与白细胞介素1A（IL1A）和MMP3基因变化的相关性，为将来基因治疗腰背痛展现了曙光。