Association Analysis of Tissue Factor Pathway Inhibitor Polymorphisms and Haplotypes with Osteonecrosis of the Femoral Head in the Korean Population

  • Dai, Xue Lian (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital) ;
  • Hong, Jung Min (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital) ;
  • Oh, Bermseok (National Genome Research Institute, National Institute of Health) ;
  • Cho, Yoon Shin (National Genome Research Institute, National Institute of Health) ;
  • Lee, Jong-Young (National Genome Research Institute, National Institute of Health) ;
  • Park, Eui Kyun (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital) ;
  • Kim, Chang Yoon (Department of Preventive Medicine, School of Medicine, Yeungnam University) ;
  • Kim, Shin-Yoon (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital) ;
  • Kim, Tae-Ho (Skeletal Diseases Genome Research Center, Kyungpook National University Hospital)
  • Received : 2008.06.10
  • Accepted : 2008.07.29
  • Published : 2008.11.30


Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1,500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.


femoral head;osteonecrosis;polymorphism;TFPI;thrombosis


Supported by : Ministry of Health and Welfare


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