Plasminogen Activator Inhibitor-1 4G/5G Polymorphism Contributes to Osteonecrosis of the Femoral Head Susceptibility: Evidence from a Systematic Review and Meta-analysis

The Plasminogen Activator Inhibitor-1 gene 4G/5G (PAI-1 4G/5G) polymorphism has been suggested to be associated with osteonecrosis of the femoral head (ONFH) susceptibility; however, the results are conflicting and inconclusive. We have carried out a comprehensive meta-analysis to derive a more precise estimation of the association. A comprehensive search in PubMed, EMBASE, Google Scholar, and ISI Web of Knowledge databases was conducted to identify all eligible case-control publications investigating the association between PAI-1 4G/5G polymorphism and ONFH risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess the association. A total of six studies with 456 cases and 1,019 controls were included in this review. Three studies were from Caucasian descendants and the three others were from East Asian descendants. Overall analysis suggests a significant association between PAI-1 4G/5G polymorphism and ONFH risk under the allele model (4G vs. 5G:OR =1.540, 95% CI =1.055-2.248, P=0.025) and the recessive model (4G4G vs. 4G5G+5G5G: OR=1.931, 95% CI:1.162-3.207, P=0.011). When stratified by ethnicity, we have found a significant association between PAI-1 4G/5G polymorphism and ONFH risk among the Caucasian (4G5G vs. 5G5G: OR=1.806, 95% CI: 1.064-3.067, P=0.029) and East Asians (4G4G vs. 5G5G: OR=1.619, 95% CI: 1.025-2.556, P=0.039 and 4G4G vs. 4G5G+5G5G: OR=1.665, 95% CI: 1.207-2.297, P=0.002). The present meta-analysis suggested that PAI-1 4G/5G (rs1799889) polymorphism is a potential risk factor for development of ONFH. However, large-scale and well-designed case-control studies in different ethnicities are required to validate these results.
Level of evidence: II