BackgroundA few months ago, the Bioscience Reports journal showed that growth differentiation factor 5 (GDF5) rs143383 genetic polymorphism increases the susceptibility of knee osteoarthritis (KOA), but previous studies’ results have debates about available data. Considering the availability of more recent data, we focus on clarifying the relationship of KOA and GDF5 rs143383 genetic polymorphism by a meta-analysis of case-control trial data.MethodsThe eligible studies from the time of database established to Oct. 2019 were collected from PubMed, Springer, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang library. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate the association between these polymorphisms and KOA risk. The meta-analysis was completed by STATA 18.0 software.ResultsA total of 196 studies were collected, 16 of them included in final meta-analysis (7997 cases and 12,684 controls). There was significant association between GDF5 rs143383 polymorphism and KOA in all genetic models (for Allele model (C versus T): OR = 0.84 (95% CI = 0.76–0.91); dominate model (CC+CT versus TT): OR = 0.80 (95% CI = 0.72–0.90); recessive model (CC versus CT+TT): OR = 0.79 (95% CI = 0.68–0.92); heterozygote model (CT versus CC+TT): OR = 0.89 (95% CI = 0.80–0.97); homozygous model (CC versus TT): OR = 0.71 (95% CI = 0.60–0.85)). In the subgroup analysis, we obtained the results that there is no significance among Asians.ConclusionGDF5 rs143383 genetic polymorphism increases the risk of KOA among Caucasians; CC genotype and C allele are protective factors for the susceptibility of KOA among Caucasians.