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

Abstract

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.

An insight into osteoarthritis susceptibility: Integration of immunological and genetic background

“…Genes that encode ADAMTS family members are also considered as novel OA candidate genes, but with inconsistent findings in different populations. A positive association between the ADAMTS5 rs2830585 genetic polymorphism and OA development was found in the Chinese population [ 69 ], while in the Turkish population no association of rs2830585 with OA susceptibility was observed [ 70 ]. The involvement of ADAMTS14 genetic polymorphisms in OA development has been also noted recently [ 71 ].…”

Expression profiles of long non‑coding RNAs in the cartilage of patients with knee osteoarthritis and normal individuals

“…The main clinical manifestations of knee osteoarthritis are slow-developing knee pain, tenderness, stiffness, joint swelling, limited mobility and knee deformity ( 8 ). The occurrence and development of knee osteoarthritis are the result of the interaction between biomechanical and biological factors, including the mechanical environment around the knee joint, the metabolic rate of the individual, the apoptosis of chondrocytes and the levels of related cytokines, such as interleukin (IL) IL-4, IL-10 and tumor necrosis factor (TNF)-α ( 9-11 ). A number of risk factors for knee osteoarthritis have been identified, including age, sex, obesity, inflammation, strain, trauma and genetics ( 12-14 ).…”

Variations of Wnt/β‐catenin pathway‐related genes in susceptibility to knee osteoarthritis: A three‐centre case‐control study

“…Osteoarthritis (OA) is the most prevalent chronic joint disease that contributes to cartilage matrix degradation . Major mechanism of OA is characterized by abnormal joint tissue metabolism and results in cartilage degradation, bone remodelling, joint inflammation, osteophyte formation and loss of normal joint function . About 9.6% of men and 18% of women ≥ 60 years old suffer from symptomatic OA worldwide .…”

“…1 Major mechanism of OA is characterized by abnormal joint tissue metabolism and results in cartilage degradation, bone remodelling, joint inflammation, osteophyte formation and loss of normal joint function. 2 About 9.6% of men and 18% of women ≥ 60 years old suffer from symptomatic OA worldwide. 3 Multiple factors, including advanced age, excessive body weight, repeated trauma or surgery to the joint structures, diabetes and hormone-related disorders, contribute to increased risk of OA.…”

“…Multiple factors, including advanced age, excessive body weight, repeated trauma or surgery to the joint structures, diabetes and hormone‐related disorders, contribute to increased risk of OA . Studies provide clear evidence of a heritable component in susceptibility of OA, but the specific genetic factors are largely unknown. It therefore remains a challenge to identify risk alleles or candidate genes that contribute to OA pathogenesis.…”