Integrative analyses of genes related to femoral head osteonecrosis: an umbrella review of systematic reviews and meta-analyses of observational studies

Abstract

Background Femoral head osteonecrosis (FHON) is a worldwide challenging clinical topic. Steroid use is one of the main etiologies of FHON. There are several genetic variants associated with FHON. Therefore, the purpose of this umbrella review was to provide a comprehensive summary of a meta-analysis and systematic review of genetic variations associated with nonsteroidal and steroid-induced FHON. Methods The eligible studies were selected from the PubMed and MEDLINE databases for the collection of diverse systematic meta-analyses and reviews. The genetic main effect score was assigned using the Human Genome Epidemiology Network's Venice criteria to assess the cumulative evidence on the effects of a single nucleotide polymorphism (SNP) on FHON. Results Eight articles reported the meta-analysis of candidate SNP-based studies covering eight genes and 13 genetic variants. In the nonsteroid-induced FHON genetic variants including rs2012390 and rs11225394 in MMP8, rs1800629 and rs361525 in tumor necrosis factor (TNF)-alpha, VNTR in intron 4, rs1799983 and rs2070744 in endothelial nitric oxide synthase (eNOS), rs2010963 in vascular endothelial growth factor (VEGF), and rs6025 in factor V showed significance in each reference. The steroid-induced FHON genetic variants including rs693 and rs1042031 in apolipoprotein (Apo)B, rs1045642 in ABCB1, and rs1799889 in PAI-1 showed significance in each reference. Conclusion Based on the systematic review conducted in this study, we organized the genomes associated with FHON and looked at each contribution. Our results could give an integrative approach for understanding the mechanism of FHON etiology. It is expected that these results could contribute to the strategy of prediagnosis, evaluating the individual risk of nonsteroid-induced and steroid-induced FHON. Level of Evidence: Level I.