Shi Xiaowei, Lv Aili, Ma Jing, Zhang Feng, Wen Yan, Zhang Zengtie, Guo Xiong
Department of Paediatrics, The First Affiliated Hospital of Medical Collage of Xi'an Jiaotong University, Xi'an, Shannxi, 710061, People's Republic of China.
School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry of Health, Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, 710061, People's Republic of China.
J Orthop Surg Res. 2016 May 31;11(1):64. doi: 10.1186/s13018-016-0398-6.
The etiology of Kashin-Beck disease (KBD), an endemic osteochondropathy, is largely unknown. Matrix metalloproteinase-1 (MMP-1) plays a central role in the initiation and progression of cartilage destruction; however, no study has reported on the relationship between KBD and MMP-1. This study was to investigate the role of MMP-1 in the pathogenesis and progression of KBD.
Single nucleotide polymorphism (SNP) genotyping was conducted for 274 KBD cases and 248 healthy controls using the Sequenom MassARRAY system. Additionally, the expression of MMP-1 in the knee articular cartilage of 22 KBD patients and 21 controls was analyzed by immunohistochemistry, and the concentration of MMP-1 in their joint fluid was also measured by enzyme-linked immunosorbent assay (ELISA).
The results showed that two SNPs (rs470221 and rs1144396) had a weak association with increased KBD risk; however, the significance of these results did not survive Bonferroni's correction. Moreover, the percentages of cells expressing MMP-1 in each layer of cartilage were significantly higher in the KBD group than in the controls (F = 11.41-28.31, P = 0.002-0.000). The concentration of MMP-1 in KBD joint fluid was significantly higher than that in the controls (t = 9.83, P < 0.0001).
The increased expression of MMP-1 has a potential effect on the risk of KBD in the northwest Chinese Han population. However, six selected SNPs in the MMP-1 gene might not be useful as significant markers for predicting KBD susceptibility in Chinese Han population. Therefore, future studies in the association of MMP-1 with KBD should focus on other candidate SNPs.
大骨节病（KBD）是一种地方性骨软骨病，其病因大多未知。基质金属蛋白酶-1（MMP-1）在软骨破坏的起始和进展中起核心作用；然而，尚无关于KBD与MMP-1关系的研究报道。本研究旨在探讨MMP-1在KBD发病机制及进展中的作用。
使用Sequenom MassARRAY系统对274例KBD患者和248例健康对照进行单核苷酸多态性（SNP）基因分型。此外，采用免疫组织化学分析22例KBD患者和21例对照的膝关节软骨中MMP-1的表达，并通过酶联免疫吸附测定（ELISA）检测其关节液中MMP-1的浓度。
结果显示，两个SNP（rs470221和rs1144396）与KBD风险增加存在弱关联；然而，这些结果的显著性未通过Bonferroni校正。此外，KBD组软骨各层中表达MMP-1的细胞百分比显著高于对照组（F = 11.41 - 28.31，P = 0.002 - 0.000）。KBD关节液中MMP-1的浓度显著高于对照组（t = 9.83，P < 0.0001）。
MMP-1表达增加对中国西北汉族人群KBD风险有潜在影响。然而，MMP-1基因中六个选定的SNP可能无法作为预测中国汉族人群KBD易感性的显著标志物。因此，未来关于MMP-1与KBD关联的研究应关注其他候选SNP。
