Molecules and Cells

  • 제26권5호
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  • Pages.490-495
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  • 2008
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

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)
  • 투고 : 2008.06.10
  • 심사 : 2008.07.29
  • 발행 : 2008.11.30
⟨ 이전 논문 다음 논문 ⟩

초록

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.

키워드

과제정보

연구 과제 주관 기관 : Ministry of Health and Welfare

참고문헌

  1. Abu-Shakra, M., Buskila, D., and Shoenfeld, Y. (2003). Osteonecrosis in patients with SLE. Clin. Rev. Allergy Immunol. 25, 13-24 https://doi.org/10.1385/CRIAI:25:1:13
  2. Aksoy, M.C., Aksoy, D.Y., Haznedaroglu, I.C., Sayinalp, N., Kirazli, S., and Alpaslan, M. (2005). Enhanced tissue factor pathway inhibitor response as a defense mechanism against ongoing local microvascular events of Legg-Calve-Perthes disease. Pediatr. Hematol. Oncol. 22, 391-399 https://doi.org/10.1080/08880010590964273
  3. Ameziane, N., Seguin, C., Borgel, D., Fumeron, F., Moatti, D., Alhenc-Gelas, M., Grandchamp, B., Aiach, M., Emmerich, J., and de Prost, D. (2002). The -33T$\rightarrow$C polymorphism in intron 7 of the TFPI gene influences the risk of venous thromboembolism, independently of the factor V Leiden and prothrombin mutations. Thromb. Haemost. 88, 195-199 https://doi.org/10.1055/s-0037-1613186
  4. Amini Nekoo, A., and Iles, D. (2008). Analysis of a T-287C polymorphism in the tissue factor pathway inhibitor gene and identification of a repressor element in the promoter. Thromb. Res. 121, 813-819 https://doi.org/10.1016/j.thromres.2007.08.012
  5. Amini-Nekoo, A., Futers, T.S., Moia, M., Mannucci, P.M., Grant, P.J., and Ariens, R.A. (2001). Analysis of the tissue factor pathway inhibitor gene and antigen levels in relation to venous thrombosis. Br. J. Haematol. 113, 537-543 https://doi.org/10.1046/j.1365-2141.2001.02752.x
  6. Assouline-Dayan, Y., Chang, C., Greenspan, A., Shoenfeld, Y., and Gershwin, M.E. (2002). Pathogenesis and natural history of osteonecrosis. Semin. Arthritis Rheum. 32, 94-124
  7. Atsumi, T., and Kuroki, Y. (1992). Role of impairment of blood supply of the femoral head in the pathogenesis of idiopathic osteonecrosis. Clin. Orthop. Relat. Res. 277, 22-30
  8. Bjorkman, A., Svensson, P.J., Hillarp, A., Burtscher, I.M., Runow, A., and Benoni, G. (2004). Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin. Orthop. Relat. Res. 425, 168-172 https://doi.org/10.1097/00003086-200408000-00023
  9. Chang, J.D., Hur, M., Lee, S.S., Yoo, J.H., and Lee, K.M. (2008). Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population. Clin. Orthop. Relat. Res. 466, 1041-1046 https://doi.org/10.1007/s11999-008-0147-1
  10. Cruess, R.L. (1986). Osteonecrosis of bone. Current concepts as to etiology and pathogenesis. Clin. Orthop. Relat. Res. 208, 30-39
  11. Fisher, D.E. (1978). The role of fat embolism in the etiology of corticosteroid- induced avascular necrosis: clinical and experimental results. Clin. Orthop. Relat. Res. 130, 68-80
  12. Girard, T.J., Warren, L.A., Novotny, W.F., Likert, K.M., Brown, S.G., Miletich, J.P., and Broze, G.J., Jr. (1989). Functional significance of the Kunitz-type inhibitory domains of lipoproteinassociated coagulation inhibitor. Nature 338, 518-520 https://doi.org/10.1038/338518a0
  13. Girard, T.J., Eddy, R., Wesselschmidt, R.L., MacPhail, L.A., Likert, K.M., Byers, M.G., Shows, T.B., and Broze, G.J., Jr. (1991). Structure of the human lipoprotein-associated coagulation inhibitor gene. Intro/exon gene organization and localization of the gene to chromosome 2. J. Biol. Chem. 266, 5036-5041
  14. Glueck, C.J., Glueck, H.I., Welch, M., Freiberg, R., Tracy, T., Hamer, T., and Stroop, D. (1994). Familial idiopathic osteonecrosis mediated by familial hypofibrinolysis with high levels of plasminogen activator inhibitor. Thromb. Haemost. 71, 195-198
  15. Glueck, C.J., Freiberg, R., Glueck, H.I., Tracy, T., Stroop, D., and Wang, Y. (1995). Idiopathic osteonecrosis, hypofibrinolysis, high plasminogen activator inhibitor, high lipoprotein(a), and therapy with Stanozolol. Am. J. Hematol. 48, 213-220 https://doi.org/10.1002/ajh.2830480402
  16. Glueck, C.J., Brandt, G., Gruppo, R., Crawford, A., Roy, D., Tracy, T., Stroop, D., Wang, P., and Becker, A. (1997a). Resistance to activated protein C and Legg-Perthes disease. Clin. Orthop. Relat. Res. 338, 139-152 https://doi.org/10.1097/00003086-199705000-00021
  17. Glueck, C.J., Freiberg, R., Tracy, T., Stroop, D., and Wang, P. (1997b). Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. Clin. Orthop. Relat. Res. 334, 43-56
  18. Glueck, C.J., Fontaine, R.N., Gruppo, R., Stroop, D., Sieve-Smith, L., Tracy, T., and Wang, P. (1999). The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin. Orthop. Relat. Res. 366, 133-146 https://doi.org/10.1097/00003086-199909000-00017
  19. Glueck, C.J., Freiberg, R.A., Fontaine, R.N., Tracy, T., and Wang, P. (2001). Hypofibrinolysis, thrombophilia, osteonecrosis. Clin. Orthop. Relat. Res. 386, 19-33 https://doi.org/10.1097/00003086-200105000-00004
  20. Gruppo, R., Glueck, C.J., McMahon, R.E., Bouquot, J., Rabinovich, B.A., Becker, A., Tracy, T., and Wang, P. (1996). The pathophysiology of alveolar osteonecrosis of the jaw: anticardiolipin antibodies, thrombophilia, and hypofibrinolysis. J. Lab. Clin. Med. 127, 481-488 https://doi.org/10.1016/S0022-2143(96)90065-7
  21. Gruppo, R., Glueck, C.J., Wall, E., Roy, D., and Wang, P. (1998). Legg-Perthes disease in three siblings, two heterozygous and one homozygous for the factor V Leiden mutation. J. Pediatr. 132, 885-888 https://doi.org/10.1016/S0022-3476(98)70326-9
  22. He, M., Wen, Z., He, X., Xiong, S., Liu, F., Xu, J., Li, J., Xie, Q., Jian, Z., Chen, F., et al. (2002). Observation on tissue factor pathway and some other coagulation parameters during the onset of acute cerebrocardiac thrombotic diseases. Thromb. Res. 107, 223-228 https://doi.org/10.1016/S0049-3848(02)00331-6
  23. Hirota, Y., Hirohata, T., Fukuda, K., Mori, M., Yanagawa, H., Ohno, Y., and Sugioka, Y. (1993). Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. Am. J. Epidemiol. 137, 530-538 https://doi.org/10.1093/oxfordjournals.aje.a116706
  24. Hong, J.M., Kim, T.H., Chae, S.C., Koo, K.H., Lee, Y.J., Park, E.K., Choi, J.Y., Ryoo, H. M., and Kim, S.Y. (2007). Association study of hypoxia inducible factor 1alpha (HIF1alpha) with osteonecrosis of femoral head in a Korean population. Osteoarthritis Cartilage 15, 688-694 https://doi.org/10.1016/j.joca.2006.12.007
  25. Jones, J.P., Jr. (1985). Fat embolism and osteonecrosis. Orthop. Clin. North Am. 16, 595-633
  26. Jones, J.P., Jr. (1999). Coagulopathies and osteonecrosis. Acta Orthop. Belg. 65, 5-8
  27. Jones, L.C., Mont, M.A., Le, T.B., Petri, M., Hungerford, D.S., Wang, P., and Glueck, C.J. (2003). Procoagulants and osteonecrosis. J. Rheumatol. 30, 783-791
  28. Kim, S.Y., Suh, J.S., Park, E.K., Jung, W.B., Kim, J.W., Koo, K.H., and Kim, C.Y. (2003). Factor V Leiden gene mutation in femoral head osteonecrosis. J. Korean Ortho. Res. Soc. 6, 259-264
  29. Kim, T.H., Hong, J.M., Park, E.K., and Kim, S.Y. (2007). Peroxisome proliferator-activated receptor-gamma gene polymorphisms are not associated with osteonecrosis of the femoral head in the Korean population. Mol. Cells 24, 388-393
  30. Lindahl, A.K. (1997). Tissue factor pathway inhibitor: from unknown coagulation inhibitor to major antithrombotic principle. Cardiovasc. Res. 33, 286-291 https://doi.org/10.1016/S0008-6363(96)00208-8
  31. Lwaleed, B.A., and Bass, P.S. (2006). Tissue factor pathway inhibitor: structure, biology and involvement in disease. J. Pathol. 208, 327-339 https://doi.org/10.1002/path.1871
  32. Miyanishi, K., Yamamoto, T., Irisa, T., Noguchi, Y., Sugioka, Y., and Iwamoto, Y. (1999). Increased level of apolipoprotein B/apolipoprotein A1 ratio as a potential risk for osteonecrosis. Ann. Rheum. Dis. 58, 514-516 https://doi.org/10.1136/ard.58.8.514
  33. Miyata, T., Sakata, T., Kumeda, K., Uchida, K., Tsushima, M., Fujimura, H., Kawasaki, T., and Kato, H. (1998). C-399T polymorphism in the promoter region of human tissue factor pathway inhibitor (TFPI) gene does not change the plasma TFPI antigen level and does not cause venous thrombosis. Thromb. Haemost. 80, 345-346 https://doi.org/10.1055/s-0037-1615202
  34. Moatti, D., Seknadji, P., Galand, C., Poirier, O., Fumeron, F., Desprez, S., Garbarz, M., Dhermy, D., Arveiler, D., Evans, A., et al. (1999). Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with acute coronary syndromes and in healthy subjects : impact of the V264M substitution on plasma levels of TFPI. Arterioscler. Thromb. Vasc. Biol. 19, 862-869 https://doi.org/10.1161/01.ATV.19.4.862
  35. Moatti, D., Haidar, B., Fumeron, F., Gauci, L., Boudvillain, O.,Seknadji, P., Olliver, V., Aumont, M.C., and de Prost, D. (2000). A new T-287C polymorphism in the 5' regulatory region of the tissue factor pathway inhibitor gene. Association study of the T-287C and C-399T polymorphisms with coronary artery disease and plasma TFPI levels. Thromb. Haemost. 84, 244-249 https://doi.org/10.1055/s-0037-1614003
  36. Mont, M.A., Ulrich, S.D., and Seyler, T.M. (2007). Role of thrombotic and fibrinolytic alterations in the pathogenesis and treatment of osteonecrosis. J. Rheumatol. 34, 466-468 https://doi.org/10.1093/rheumatology/34.5.466
  37. Nilsson, I.M., Krook, H., Sternby, N.H., Soderberg, E., and Soderstrom, N. (1961). Severe thrombotic disease in a young man with bone marrow and skeletal changes and with a high content of an inhibitor in the fibrinolytic system. Acta Med. Scand. 169, 323-337 https://doi.org/10.1111/j.0954-6820.1961.tb07838.x
  38. Qin, Z.S., Niu, T., and Liu, J.S. (2002). Partition-ligation-expectation- maximization algorithm for haplotype inference with singlenucleotide polymorphisms. Am. J. Hum. Genet. 71, 1242-1247 https://doi.org/10.1086/344207
  39. Rapaport, S.I., and Rao, L.V. (1995). The tissue factor pathway: how it has become a "prima ballerina". Thromb. Haemost. 74, 7-17
  40. Saito, S., Ohzono, K., and Ono, K. (1992). Early arteriopathy and postulated pathogenesis of osteonecrosis of the femoral head. The intracapital arterioles. Clin. Orthop. Relat. Res. 277, 98-110
  41. Van Veldhuizen, P.J., Neff, J., Murphey, M.D., Bodensteiner, D., and Skikne, B.S. (1993). Decreased fibrinolytic potential in patients with idiopathic avascular necrosis and transient osteoporosis of the hip. Am. J. Hematol. 44, 243-248 https://doi.org/10.1002/ajh.2830440405
  42. Wang, Y., Li, Y., Mao, K., Li, J., Cui, Q., and Wang, G.J. (2003). Alcohol-induced adipogenesis in bone and marrow: a possible mechanism for osteonecrosis. Clin. Orthop. Relat. Res. 410, 213-224 https://doi.org/10.1097/01.blo.0000063602.67412.83
  43. Wermes, C., Bergmann, F., Reller, B., and Sykora, K.W. (1999). Severe protein C deficiency and aseptic osteonecrosis of the hip joint: a case report. Eur. J. Pediatr. 158(Suppl. 3), S159-161 https://doi.org/10.1007/PL00014345
  44. Zalavras, C.G., Malizos, K.N., Dokou, E., and Vartholomatos, G. (2002). The 677C$\rightarrow$T mutation of the methylene-tetrahydrofolate reductase gene in the pathogenesis of osteonecrosis of the femoral head. Haematologica 87, 111-112
  45. Zalavras, C.G., Vartholomatos, G., Dokou, E., and Malizos, K.N. (2004). Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin. Orthop. Relat. Res. 422, 251-255 https://doi.org/10.1097/01.blo.0000127921.13253.e3