Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head
نویسندگان
چکیده
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.
منابع مشابه
Plasminogen Activator Inhibitor-1 4G/5G Polymorphism Contributes to Osteonecrosis of the Femoral Head Susceptibility: Evidence from a Systematic Review and Meta-analysis
Background: The Plasminogen Activator Inhibitor-1 gene 4G/5G (PAI-1 4G/5G) polymorphism has been suggestedto be associated with osteonecrosis of the femoral head (ONFH) susceptibility; however, the results are conflicting andinconclusive. We have carried out a comprehensive meta-analysis to derive a more precise estimation of the association.Methods: A comprehensive search in PubMed, EMBASE, Go...
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