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

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.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).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.Osteonecrosis of the femoral head (ONFH) is a devastating bone disease in which patients experience progressive collapse of the femoral head caused by a disturbance in the supply of blood and anomalies in the fibrinolytic system [1,2]. An increased tendency for intravascular coagulation is proposed as the pathogenetic mechanism responsible for interruption of the osseous blood supply and ONFH, and a significantly higher prevalence of coagulation abnormalities is reported in patients with ONFH [1,3]. Recent studies have suggested that genetic polymorphisms in factor V, prothrombin, methylenetetrahydrofolate reductase (MTHFR), and plasminogen activator inhibitor-1 (PAI-1) genes leading to intravascular coagulation disorders may be related to ONFH [4-6].PAI-1 is a critical factor that regulates coagulation and fibrinol