Genetic variation of aggrecanase-2 (ADAMTS5) in susceptibility to osteoarthritis

Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model. We aimed to investigate the effects of ADAMTS5 gene polymorphisms on OA risk in a Chinese population. A total of 300 OA patients and 300 controls were recruited and their genotypes for ADAMTS5 gene rs226794 and rs2830585 polymorphisms were determined using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ kit. ADAMTS5-associated genes were identified by co-expression analysis and their functions were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Bioinformatics analysis showed that ADAMTS5 was significantly related to the components, structural constituent, and organization of the extracellular matrix. The rs2830585 polymorphism, but not rs226794 polymorphism, was significantly associated with an increased risk of knee OA. Stratified analysis further confirmed this significant association in patients at age ≥55 years. In conclusion, the ADAMTS5 rs2830585 polymorphism may be involved in the development of knee OA by destroying the extracellular matrix, but this finding should be further confirmed by larger studies.

聚集蛋白聚糖酶-2（ADAMTS5）基因可介导聚集蛋白聚糖降解，该过程可能参与小鼠骨关节炎（OA）模型中的软骨破坏。本研究旨在探究中国人群中ADAMTS5基因多态性对OA发病风险的影响。研究共招募300名OA患者与300名健康对照，采用定制化48重单核苷酸多态性扫描（custom-by-design 48-Plex single nucleotide polymorphism Scan™）试剂盒，对ADAMTS5基因rs226794及rs2830585多态性位点进行基因分型。通过共表达分析筛选ADAMTS5相关基因，并借助基因本体（Gene Ontology, GO）富集分析与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析探究其功能。生物信息学分析显示，ADAMTS5与细胞外基质的组成成分、结构功能及组织构建显著相关。rs2830585多态性（而非rs226794多态性）与膝OA发病风险升高存在显著关联；分层分析进一步证实，该关联在年龄≥55岁的患者亚组中依然显著。综上，ADAMTS5 rs2830585多态性可能通过破坏细胞外基质参与膝OA的发生发展，但该结论尚需更大规模的研究予以进一步验证。