ADAMTS-1, ADAMTS-5 and ADAMTS-13 are considered potential targets in the treatment of frozen shoulder.

Abstract

Frozen shoulder (FS) is a condition that causes shoulder pain and restricted movement, primarily due to inflammation, fibrosis, and adhesion of the shoulder joint capsule. It commonly affects individuals aged 30 to 60 years. Factors such as diabetes, obesity, and shoulder trauma are known risk factors. Although current treatments include nonsteroidal anti-inflammatory drugs, steroid injections, and physical therapy, approximately 22.5% of patients do not respond well to conservative treatments and may require surgical intervention. The ADAMTS family is thought to play a significant role in joint diseases, and this study investigates its impact on FS. This study employed the Mendelian Randomization (MR) analysis method using genome-wide association studies (GWAS) data to analyze the causal relationships between the ADAMTS-5 and ADAMTS-13 genes and FS. By screening SNPs related to ADAMTS-1, ADAMTS-5, and ADAMTS-13, data analysis was performed using R software to verify the impact of these genes on FS pathogenesis. Additionally, co-location analysis was conducted to identify potential therapeutic targets. The MR analysis results indicate that ADAMTS-1-mediated ADAMTS-5 levels, along with the levels of ADAMTS-5 and ADAMTS-13 themselves, significantly increase the risk of FS. Co-expression localization analysis revealed that rs62217270, rs977151, and rs4962153 are potential targets for inhibiting ADAMTS-1, ADAMTS-5, and ADAMTS-13, respectively. In our study, ADAMTS-1, ADAMTS-5, and ADAMTS-13 were identified as potential risk factors contributing to the development of FS. The SNP rs62217270 may serve as a potential therapeutic target for FS by downregulating ADAMTS-5 expression through inhibition of ADAMTS-1. Additionally, rs977151 and rs4962153 were identified as potential targets for FS treatment via the reduction of ADAMTS-5 and ADAMTS-13 levels, respectively.