• 上海交通大學(xué)附屬第六人民醫(yī)院骨科（上海，200233）;

目的 綜述遺傳性高凝狀態(tài)（heritable hypercoagulable state， HHCS）與股骨頭缺血性壞死（avascular necrosis of femoral head，ANFH）相關(guān)性的研究進(jìn)展。 方法 廣泛查閱近年有關(guān)HHCS 相關(guān)基因突變與ANFH 關(guān)系的文獻(xiàn)，并總結(jié)分析。 結(jié)果 研究表明，凝血因子Ⅴ基因G1691A、凝血酶原基因G20210A、5，10- 亞甲基四氫葉酸還原酶基因C677T、纖溶酶原激活物抑制物1 基因4G/5G 以及組織因子途徑抑制劑基因等多種HHCS 相關(guān)基因突變與ANFH存在一定關(guān)系。 結(jié)論 HHCS 可能是ANFH 的遺傳學(xué)易感因素，HHCS 在我國(guó)ANFH 發(fā)生發(fā)展中所發(fā)揮的作用有待進(jìn)一步研究明確。

引用本文： 殷文靖,盛加根. 遺傳性高凝狀態(tài)與股骨頭缺血性壞死相關(guān)性研究進(jìn)展. 中國(guó)修復(fù)重建外科雜志, 2012, 26(6): 695-698. doi: 復(fù)制

1. Jones JP Jr. Intravascular coagulation and osteonecrosis. Clin Orthop Relat Res, 1992, (277): 41-53.
2. Guan XY, Han D. Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci, 2010, 15 (3): 365-370.
3. Miyata N, Kumagai K, Osaki M, et al. Pentosan reduces osteonecrosis of femoral head in SHRSP. Clin Exp Hypertens, 2010, 32 (8): 511-516.
4. Norman D, Miller Y, Sabo E, et al. The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat. APMIS, 2002, 110 (3): 221-228.
5. Boss JH, Misselevich I, Bejar J, et al. Experimentally gained insight-based proposal apropos the treatment of osteonecrosis of the femoral head. Med Hypotheses, 2004, 62 (6): 958-965.
6. Glueck CJ, Freiberg RA, Sieve L, et al. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res, 2005, (435): 164-170.
7. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 1994, 369 (6475): 64-67.
8. Poort SR, Rosendaal FR, Reitsma PH, et al. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood, 1996, 88 (10): 3698-3703.
9. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol, 2007, 44 (2): 62-69.
10. Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood, 2008, 112 (1): 19-27.
11. Glueck CJ, Goldenberg N, Budhani S, et al. Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. Transl Res, 2011, 158 (4): 225-234.
12. Bjorkman A, Svensson PJ, Hillarp A, et al. Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res, 2004, (425): 168-172.
13. Zalavras CG, Vartholomatos G, Dokou E, et al. Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin Orthop Relat Res, 2004, (422): 251-255.
14. Vosmaer A, Pereira RR, Koenderman JS, et al. Coagulation abnormalities in Legg-Calvé-Perthes disease. J Bone Joint Surg (Am), 2010, 92 (1): 121-128.
15. Chang JD, Hur M, Lee SS, et al. Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population. Clin Orthop Relat Res, 2008, 466 (5): 1041-1046.
16. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 1995, 10 (1): 111-113.
17. Zalavras CG, Malizos KN, Dokou E, et al. The 677C→T mutation of the methylene-tetrahydrofolate reductase gene in the pathogenesis of osteonecrosis of the femoral head. Haematologica, 2002, 87 (1): 111-112.
18. 劉丙立, 李子榮, 孫偉, 等. 酒精性股骨頭壞死與亞甲基四氫葉酸還原酶 677 C/T單核苷酸多態(tài)性的關(guān)系. 中國(guó)修復(fù)重建外科雜志, 2009, 23 (9): 1079-1082.
19. Glueck CJ, Freiberg RA, Fontaine RN, et al. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res, 2001, (386): 19-33.
20. da Silva LR, Vergani N, Galdieri Lde C, et al. Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in Brazil. Am J Med Genet A, 2005, 135 (3): 263-267.
21. Juo SH, Liao YC, Kuo CL, et al. The MTHFR 677 C/T polymorphism influences plasma levels of adhesion molecules and nitric oxide. Thromb Res, 2008, 121 (4): 549-554.
22. Kim TH, Hong JM, Kim HJ, et al. Lack of association of MTHFR gene polymorphisms with the risk of osteonecrosis of the femoral head in a Korean population. Mol Cells, 2010, 29 (4): 343-348.
23. Dawson SJ, Wiman B, Hamsten A, et al. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem, 1993, 268 (15): 10739-10745.
24. Glueck CJ, Fontaine RN, Gruppo R, et al. The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin Orthop Relat Res, 1999, (366): 133-146.
25. Ferrari P, Schroeder V, Anderson S, et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation, 2002, 74 (8): 1147-1152.
26. Tan X, Cai D, Wu Y, et al. Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. Transl Res, 2006, 148 (3): 114-119.
27. Asano T, Takahashi KA, Fujioka M, et al. Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation, 2004, 77 (2): 220-225.
28. Dai XL, Hong JM, Oh B, et al. Association analysis of tissue factor pathway inhibitor polymorphisms and haplotypes with osteonecrosis of the femoral head in the Korean population. Mol Cells, 2008, 26 (5): 490-495.
29. Séguin C, Kassis J, Busque L, et al. Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia. Rheumatology (Oxford), 2008, 47 (8): 1151-1155.
30. Zakai NA, McClure LA. Racial differences in venous thromboembolism. J Thromb Haemost, 2011, 9 (10): 1877-1882.
31. Pandey SK, Meena A, Kishor K, et al. Prevalence of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210A among asian Indian Sickle Cell patients. Clin Appl Thromb Hemost, 2011, 18 (3): 320-323.
32. Mazoyer E, Ripoll L, Gueguen R, et al. Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution. Blood Coagul Fibrinolysis, 2009, 20 (7): 503-510.
33. Al-Sweedan SA, Jaradat S, Iraqi M, et al. The prevalence of factor V Leiden (G1691A), prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations in Jordanian patients with beta-thalassemia major. Blood Coagul Fibrinolysis, 2009, 20 (8): 675-678.
34. Dashti AA, Jadaon MM. Race differences in the prevalence of the factor V Leiden mutation in Kuwaiti nationals. Mol Biol Rep, 2011, 38 (6): 3623-3628.
  1. 1. Jones JP Jr. Intravascular coagulation and osteonecrosis. Clin Orthop Relat Res, 1992, (277): 41-53.
  2. 2. Guan XY, Han D. Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci, 2010, 15 (3): 365-370.
  3. 3. Miyata N, Kumagai K, Osaki M, et al. Pentosan reduces osteonecrosis of femoral head in SHRSP. Clin Exp Hypertens, 2010, 32 (8): 511-516.
  4. 4. Norman D, Miller Y, Sabo E, et al. The effects of enoxaparin on the reparative processes in experimental osteonecrosis of the femoral head of the rat. APMIS, 2002, 110 (3): 221-228.
  5. 5. Boss JH, Misselevich I, Bejar J, et al. Experimentally gained insight-based proposal apropos the treatment of osteonecrosis of the femoral head. Med Hypotheses, 2004, 62 (6): 958-965.
  6. 6. Glueck CJ, Freiberg RA, Sieve L, et al. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res, 2005, (435): 164-170.
  7. 7. Bertina RM, Koeleman BP, Koster T, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 1994, 369 (6475): 64-67.
  8. 8. Poort SR, Rosendaal FR, Reitsma PH, et al. A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood, 1996, 88 (10): 3698-3703.
  9. 9. Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol, 2007, 44 (2): 62-69.
  10. 10. Dahlbäck B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood, 2008, 112 (1): 19-27.
  11. 11. Glueck CJ, Goldenberg N, Budhani S, et al. Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. Transl Res, 2011, 158 (4): 225-234.
  12. 12. Bjorkman A, Svensson PJ, Hillarp A, et al. Factor V leiden and prothrombin gene mutation: risk factors for osteonecrosis of the femoral head in adults. Clin Orthop Relat Res, 2004, (425): 168-172.
  13. 13. Zalavras CG, Vartholomatos G, Dokou E, et al. Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin Orthop Relat Res, 2004, (422): 251-255.
  14. 14. Vosmaer A, Pereira RR, Koenderman JS, et al. Coagulation abnormalities in Legg-Calvé-Perthes disease. J Bone Joint Surg (Am), 2010, 92 (1): 121-128.
  15. 15. Chang JD, Hur M, Lee SS, et al. Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population. Clin Orthop Relat Res, 2008, 466 (5): 1041-1046.
  16. 16. Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet, 1995, 10 (1): 111-113.
  17. 17. Zalavras CG, Malizos KN, Dokou E, et al. The 677C→T mutation of the methylene-tetrahydrofolate reductase gene in the pathogenesis of osteonecrosis of the femoral head. Haematologica, 2002, 87 (1): 111-112.
  18. 18. 劉丙立, 李子榮, 孫偉, 等. 酒精性股骨頭壞死與亞甲基四氫葉酸還原酶 677 C/T單核苷酸多態(tài)性的關(guān)系. 中國(guó)修復(fù)重建外科雜志, 2009, 23 (9): 1079-1082.
  19. 19. Glueck CJ, Freiberg RA, Fontaine RN, et al. Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res, 2001, (386): 19-33.
  20. 20. da Silva LR, Vergani N, Galdieri Lde C, et al. Relationship between polymorphisms in genes involved in homocysteine metabolism and maternal risk for Down syndrome in Brazil. Am J Med Genet A, 2005, 135 (3): 263-267.
  21. 21. Juo SH, Liao YC, Kuo CL, et al. The MTHFR 677 C/T polymorphism influences plasma levels of adhesion molecules and nitric oxide. Thromb Res, 2008, 121 (4): 549-554.
  22. 22. Kim TH, Hong JM, Kim HJ, et al. Lack of association of MTHFR gene polymorphisms with the risk of osteonecrosis of the femoral head in a Korean population. Mol Cells, 2010, 29 (4): 343-348.
  23. 23. Dawson SJ, Wiman B, Hamsten A, et al. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem, 1993, 268 (15): 10739-10745.
  24. 24. Glueck CJ, Fontaine RN, Gruppo R, et al. The plasminogen activator inhibitor-1 gene, hypofibrinolysis, and osteonecrosis. Clin Orthop Relat Res, 1999, (366): 133-146.
  25. 25. Ferrari P, Schroeder V, Anderson S, et al. Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transplantation, 2002, 74 (8): 1147-1152.
  26. 26. Tan X, Cai D, Wu Y, et al. Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. Transl Res, 2006, 148 (3): 114-119.
  27. 27. Asano T, Takahashi KA, Fujioka M, et al. Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transplantation, 2004, 77 (2): 220-225.
  28. 28. Dai XL, Hong JM, Oh B, et al. Association analysis of tissue factor pathway inhibitor polymorphisms and haplotypes with osteonecrosis of the femoral head in the Korean population. Mol Cells, 2008, 26 (5): 490-495.
  29. 29. Séguin C, Kassis J, Busque L, et al. Non-traumatic necrosis of bone (osteonecrosis) is associated with endothelial cell activation but not thrombophilia. Rheumatology (Oxford), 2008, 47 (8): 1151-1155.
  30. 30. Zakai NA, McClure LA. Racial differences in venous thromboembolism. J Thromb Haemost, 2011, 9 (10): 1877-1882.
  31. 31. Pandey SK, Meena A, Kishor K, et al. Prevalence of Factor V Leiden G1691A, MTHFR C677T, and Prothrombin G20210A among asian Indian Sickle Cell patients. Clin Appl Thromb Hemost, 2011, 18 (3): 320-323.
  32. 32. Mazoyer E, Ripoll L, Gueguen R, et al. Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution. Blood Coagul Fibrinolysis, 2009, 20 (7): 503-510.
  33. 33. Al-Sweedan SA, Jaradat S, Iraqi M, et al. The prevalence of factor V Leiden (G1691A), prothrombin G20210A and methylenetetrahydrofolate reductase C677T mutations in Jordanian patients with beta-thalassemia major. Blood Coagul Fibrinolysis, 2009, 20 (8): 675-678.
  34. 34. Dashti AA, Jadaon MM. Race differences in the prevalence of the factor V Leiden mutation in Kuwaiti nationals. Mol Biol Rep, 2011, 38 (6): 3623-3628.