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Molecular and genetic predictors of the requirement for joint replacement in rheumatoid arthritis

Jenvey, Cara Angharad

Molecular and genetic predictors of the requirement for joint replacement in rheumatoid arthritis Thumbnail


Authors

Cara Angharad Jenvey



Contributors

Samantha Hider
Supervisor

Derek Mattey
Supervisor

John R Glossop
Supervisor

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease of the synovial joints leading to progressive joint destruction and functional impairment. As a result of joint damage many RA patients will undergo total joint replacement. The aim of this study was to investigate the relationship of clinical variables, biomarkers and genetic polymorphisms with total joint replacement in RA.

Patients were recruited from a prospective cohort study established at the Haywood Rheumatology Centre. Patients fulfilling 1987 ARA Criteria for RA were followed up annually in clinic for 5 years. Case notes were reviewed retrospectively to determine if a patient had undergone joint replacement surgery. Clinical factors associated with baseline joint replacement included age, mechanical joint score and treatment with biological therapies. At 5 year follow up, age, disease duration, treatment with biologics and COX-1 and 2 inhibitors, the presence of erosions on baseline x-ray imaging and mechanical joint score were predictive of a new joint replacement. In terms of biomarkers, a strong association between baseline levels of MMP-3 and joint replacement at 5 years was observed. Following multivariate analysis, associations were also found between baseline levels of MMP-1, angiopoietin and HGF and joint replacement at 5 years. At baseline, high levels of TGF-β were associated with joint replacement. High levels of follistatin and GCSF and anti-CCP positivity were found to be associated with a reduced rate of joint replacement surgery.

Thirdly, a number of candidate genetic polymorphisms were analysed. The TGF-β TC allele on codon 10 was found to be protective against requiring a joint replacement. Despite the influence of TGF-β genotype and levels on surgery there was no correlation found between TGF-β genotype and TGF-β levels in the study sample.

In conclusion, this thesis demonstrates that a number of biomarkers including HGF, ANGPT-1, MMPs 1 and 3 and TGF-β are associated with joint replacement and may play a role in joint destruction in RA.

Citation

Jenvey, C. A. (2016). Molecular and genetic predictors of the requirement for joint replacement in rheumatoid arthritis. (Thesis). Keele University. Retrieved from https://keele-repository.worktribe.com/output/827982

Thesis Type Thesis
Deposit Date May 15, 2024
Publicly Available Date May 15, 2024
Public URL https://keele-repository.worktribe.com/output/827982
Award Date 2016-03

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Copyright Statement
This electronic version of the thesis has been edited solely to ensure compliance with copyright legislation and excluded material is referenced in the text. The full, final, examined and awarded version of the thesis is held by the University Library.





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