1 Department of Orthopedics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Orthopedics, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Department of Pathology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

4 Department of Radiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

5 Department of Emergency Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

6 Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


Background: 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.
Methods: 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.
Results: 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).
Conclusion: 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


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