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Background  Osteoarthritis (OA) is a degenerative joint disease with a complex genetic background. Variants in growth differentiation factor 5 ( GDF5 ) have been reported to be associated with rheumatoid arthritis (RA) in several ethnic populations. The present study aimed to assess the association between the  GDF5 +104T/C  polymorphism and the susceptibility of the knee to OA through a meta-analysis of available case-control studies.    Methods  The PubMed and Science Direct citation databases were used to search electronic literature in order to identify studies published between January 2007 and July 2016 that evaluated the association between the  GDF5 +104T/C  polymorphism and the susceptibility of the knee to OA. Different genetic models were used to assess the pooled and stratified data.    Results  A positive association was found in all pooled studies (OR = 0.808, 95 % CI = 0.754–0.866,  p  < 0.001). Regarding genotypes, significant associations were found using a dominant model (OR = 0.777, 95 % CI = 0.708–0.852,  p  < 0.001), a recessive model (OR = 0.723, 95%CI = 0.623–0.839,  p  < 0.001), and an additive model ( CC  vs  TT  OR = 0.648, 95 % CI = 0.552–0.760,  p  < 0.001;  CC  vs  CT  OR = 0.801, 95 % CI = 0.685–0.936,  p  = 0.005). Meta-analysis data were stratified by ethnicity, and the  GDF5 C  allele was found to be positively associated with OA of the knee in both Caucasians and Asians, as were the  GDF5 TC  and  CC  genotypes. In addition, using an additive model, the  CC  genotype was found to be significantly associated with OA of the knee in both Caucasians and Asians when comparing  CC  vs  TT  genotypes, but not in Caucasians when comparing  TT  vs  CT  genotypes.    Conclusions  Meta-analysis results indicated that the  GDF5 +104T/C  polymorphism is a protective factor for OA among Caucasian and Asian populations.

journal of orthopaedic surgery and research

Association between GDF5 +104T/C polymorphism and knee osteoarthritis in Caucasian and Asian populations: a meta-analysis based on case-control studies