Correlation between growth differentiation factor 5 (rs143383) gene polymorphism and knee osteoarthritis: an updated systematic review and meta-analysis

BACKGROUND: A great deal of evidence has supported that growth differentiation factor 5 (GDF5) is associated with the occurrence of knee osteoarthritis (KOA), while their results are not consistent. In the present study, we aimed to explore the association between GDF5 gene polymorphism and KOA for a more credible conclusion. METHODS: Comprehensive literature searches were carried out in English databases, including PubMed, Embase, Web of Science (WOS), and Cochrane, and Chinese databases, including China National Knowledge Infrastructure (CNKI), WANFANG, and VIP database. After the data were extracted from the required studies, the odds ratios (ORs) and their 95% confidence intervals (CIs) were determined to assess the correlation between GDF5 gene polymorphism and KOA. The publication bias was evaluated by funnel plot. RESULTS: According to the inclusion and exclusion criteria, 15 studies on the correlation between GDF5 gene polymorphism and KOA occurrence were eligible for meta-analysis. Among these articles, four studies showed no apparent correlation, while the other 11 studies indicated an obvious correlation. Meanwhile, we also carried out a subgroup analysis of the population. Due to the inevitable heterogeneity, three genetic models were finally selected for analysis. With the allele model (C versus T: OR = 0.79, 95% CI = 0.73~0.87), recessive model (CC versus CT + TT: OR = 0.76, 95% CI = 0.68~0.86), and homozygous model (CC versus TT: OR = 0.66, 95% CI = 0.58~0.76), GDF5 gene polymorphism decreased the risk of KOA. Besides, a significant association was observed in Caucasians, Asians, and Africans. Meanwhile, the protective effect of genotype C (or CC) in the Asian group was little obvious than that in the Caucasian group and the African group. Although the quality of the included studies was above medium-quality, we obtained results with a low level of evidence. CONCLUSIONS: The results of the meta-analysis showed that the genotype C (or CC) of GDF5 protected against KOA occurrence in Caucasian, Asian, and African populations.