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Open Access Research article

Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head

Hye- Ok Kim12, Chang- Hoon Cho12, Yoon- Je Cho3, Seong- Ho Cho14, Kyung- Sik Yoon12 and Kang- Il Kim3*

Author Affiliations

1 Department of Biochemistry and Molecular Biology (BK21 project), Kyung Hee University School of Medicine, Seoul, 130-701, Korea

2 MRC for Bioreaction to ROS and Biomedical Science Institute Kyung Hee University School of Medicine, Seoul, 130-701, Korea

3 Department of Orthopaedic Surgery, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, 134-727, Korea

4 Division of Allergy-Immunology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

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BMC Musculoskeletal Disorders 2011, 12:160  doi:10.1186/1471-2474-12-160

Published: 14 July 2011

Abstract

Background

The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk.

Methods

Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan® 5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH.

Results

The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001).

Conclusion

Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.