Association between genetic polymorphisms and osteoarthritis development. Overview of systematic reviews.

Objective: To identify, critically evaluate and synthesize the evidence obtained from systematic reviews on the association between genetic polymorphisms and osteoarthritis (OA) development.

Methods: Considering gene polymorphisms associated with OA susceptibility (risk or protection), a comprehensive search was conducted in the following databases, without date or language restrictions: MEDLINE, via Pubmed; Embase, via Elsevier; Cochrane Database of Systematic Reviews, via Wiley; Biblioteca Virtual em Saúde. Gray literature was also searched through the OpenGrey database. The AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews) was used to assess the methodological quality of the included systematic reviews.

Results: We included 14 systematic reviews of case-control studies comparing individuals with a radiographic diagnosis of all OA types and healthy controls, all submitted to the genetic examination of different polymorphisms in candidate genes. Meta-analyses showed a protective effect against knee and hand OA associated with GDF-5 gene (odds ratio [OR] 0.90, 95% confidence interval (CI) 0.85-0.95), and knee OA with ESRα gene (OR 0.63, 95% CI 1.26-1.97). SMAD3 gene was associated with knee and hip OA risk (OR 1.21. 95% CI 1.07-1.38) and MMP-1 gene was associated with temporomandibular OA (OR 1.58. 95% CI 1.26-1.97).

Conclusion: Based on low-quality to critically-low-quality systematic reviews, some gene polymorphisms seem to be associated with risk or protection for OA. Further high-quality studies are needed to validate these hypotheses, contribute to disease understanding, and possibly help the decision-making related to early diagnosis and treatment options for OA. PROSPERO register CRD42021234231.