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

Abstract

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.

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

“…On the other hand, the C allele of GDF‐5 (rs143383) seems to be associated with protection against knee OA and/or hand OA. Also, the results showed that the allele C (or genotype CC) of the GDF‐5 polymorphism (rs143383) protected against knee OA occurrence in Caucasian, Asian, and African populations 8,29,31 …”

“…Also, the results showed that the allele C (or genotype CC) the GDF-5 polymorphism (rs143383) protected against knee OA occurrence in Caucasian, Asian, and African populations. 8,29,31 The estrogen receptor α (ESRα) gene regulates cellular signal pathways in vivo and bone mass in skeletal systems. Moreover, human ESRα, a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulates gene expression and function, is one of the critical mediators of hormonal response in estrogen-sensitive tissues.…”

“…In addition, some of these polymorphisms may be specific to OA subtypes (hip, knee, or hand) and ethnic groups. [7][8][9] Although the importance of some genes in OA pathogenesis is relatively well established, the association of polymorphisms with susceptibility to OA was not consistent because of the heterogeneity and complexity of this disease. Therefore, given the growing interest of clinicians and researchers in polymorphisms associated with OA and the large number of systematic reviews published so far, it is necessary to synthesize this information to facilitate the access and dissemination of knowledge, as well as to assess the methodological quality of these reviews to quantify confidence in the evidence for the support of decisionmaking.…”

“…Recent systematic reviews have assessed observational studies that addressed polymorphisms in numerous candidate genes, searching for an association that could indicate susceptibility to risk or protection in OA development. In addition, some of these polymorphisms may be specific to OA subtypes (hip, knee, or hand) and ethnic groups 7–9 . Although the importance of some genes in OA pathogenesis is relatively well established, the association of polymorphisms with susceptibility to OA was not consistent because of the heterogeneity and complexity of this disease.…”

Osteoarthritis year in review: genetics, genomics, epigenetics

“…The GDF5 polymorphism rs143383 is reproducibly associated with OA, and this year was associated with OA-risk in the Kurdish population 1 . Oddly, in two meta-analyses examining the association of rs143383 with knee OA (KOA) in Asian individuals contradictory findings were observed 2,3 , while a new study in a Chinese Han population did find a link with KOA 4 . rs143383 is located in the 5 0 UTR of GDF5 and is associated with differential allelic expression of the gene, via altered DNA-binding of several transcriptional repressors 5 .…”