Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population

Diagnostic Pathology

Na Lin²  Weiheng Chen³  Zhiyao Wang³  Xiangying Kong²  Shangzhu Li¹  Rongtian Wang³  Yanqiong Zhang² 

[1] Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300041, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China;Wang Jing Hospital (Hospital of Orthopedics and Traumatology), China Academy of Chinese Medical Sciences, Beijing 100102, China

关键词: Single nucleotide polymorphism;    Plasminogen activator inhibitor-1;    Steroid-induced osteonecrosis of the femoral head;   

Others  :  804328
DOI  :  10.1186/1746-1596-8-169

 received in 2013-10-03, accepted in 2013-10-08,  发布年份 2013

【 摘 要 】

Background

Steroid usage has been considered as a leading cause of non-traumatic osteonecrosis of the femoral head (ONFH), which is involved in hypo-fibrinolysis and blood supply interruption. Genetic polymorphisms in plasminogen activator inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in several populations. However, this relationship has not been established in Chinese population. The aim of this study was to investigate the association of PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese population.

Methods

A case–control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs11178 and rs2227631) within PAI-1 were genotyped using Sequenom MassARRAY system.

Results

rs2227631 SNP was significantly associated with steroid-induced ONFH group in codominant (P = 0.04) and recessive (P = 0.02) models. However, there were no differences found in genotype frequencies of rs11178 SNP between controls and patients with steroid-induced ONFH (all P > 0.05).

Conclusions

Our data offer the convincing evidence for the first time that rs2227631 SNP of PAI-1 may be associated with the risk of steroid-induced ONFH, suggesting that the genetic variations of this gene may play an important role in the disease development.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1569909986109783 webcite.

【 授权许可】

   
2013 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Balla B, Pintér C, Kósa JP, Podani J, Takács I, Nagy Z, Speer G, Horváth B, Korányi L, Lakatos P: Gene expression changes in femoral head necrosis of human bone tissue. Dis Markers 2011, 31:25-32.
• [2]Chang JD, Hur M, Lee SS, Yoo JH, Lee KM: Genetic background of nontraumatic osteonecrosis of the femoral head in the Korean population. Clin Orthop Relat Res 2008, 466:1041-1046.
• [3]Asano T, Takahashi KA, Fujioka M, Inoue S, Satomi Y, Nishino H, Tanaka T, Hirota Y, Takaoka K, Nakajima S, Kubo T: Genetic analysis of steroid-induced osteonecrosis of the femoral head. J Orthop Sci 2003, 8:329-333.
• [4]Petcu EB, Ivanovski S, Wright RG, Slevin M, Miroiu RI, Rinzaniuc K: Bisphosphonate-related osteonecrosis of jaw (BRONJ): an anti-angiogenic side-effect? Diagn Pathol 2012, 7:78. BioMed Central Full Text
• [5]Miller IJ, Blank A, Yin SM, Mcnickle A, Gray R, Gitelis S: A case of recurrent giant cell tumor of bone with malignant transformation and benign pulmonary metastases. Diagn Pathol 2010, 5:62. BioMed Central Full Text
• [6]Kuribayashi M, Fujioka M, Takahashi KA, Arai Y, Hirata T, Nakajima S, Yoshimura N, Satomi Y, Nishino H, Kondo K, Fukushima W, Hirota Y, Kubo T: Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head. J Orthop Sci 2008, 13:297-303.
• [7]Lee YJ, Lee JS, Kang EH, Lee YK, Kim SY, Song YW, Koo KH: Vascular endothelial growth factor polymorphisms in patients with steroid-induced femoral head osteonecrosis. J Orthop Res 2012, 30:21-27.
• [8]Tamura K, Nakajima S, Hirota Y, Takahashi KA, Fujioka M, Kubo T, Iwatani Y, Ozono K: Genetic association of a polymorphism of the cAMP-responsive element binding protein-binding protein with steroid-induced osteonecrosis after kidney transplantation. J Bone Miner Metab 2007, 25:320-325.
• [9]Guan XY, Han D: Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci 2010, 15:365-370.
• [10]Wang G, Zhang CQ, Sun Y, Feng Y, Chen SB, Cheng XG, Zeng BF: Changes in femoral head blood supply and vascular endothelial growth factor in rabbits with steroid-induced osteonecrosis. J Int Med Res 2010, 38:1060-1069.
• [11]Fortenberry YM: Plasminogen activator inhibitor-1 inhibitors: a patent review (2006 - present). Expert Opin Ther Pat 2013, 23:801-815.
• [12]Singh NK, Gupta A, Behera DR, Dash D: Elevated plasminogen activator inhibitor type-1 (PAI-1) as contributing factor in pathogenesis of hypercoagulable state in antiphospholipid syndrome. Rheumatol Int 2013, 33:2331-2336.
• [13]Declerck PJ, Gils A: Three decades of research on plasminogen activator inhibitor-1: a multifaceted serpin. Semin Thromb Hemost 2013, 39:356-364.
• [14]Tan X, Cai D, Wu Y, Liu B, Rong L, Chen Z, Zhao Q: Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head. Transl Res 2006, 148:114-119.
• [15]Hozumi A, Osaki M, Sakamoto K, Goto H, Fukushima T, Baba H, Shindo H: Dexamethasone-induced plasminogen activator inhibitor-1 expression in human primary bone marrow adipocytes. Biomed Res 2010, 31:281-286.
• [16]Sakamoto K, Osaki M, Hozumi A, Goto H, Fukushima T, Baba H, Shindo H: Simvastatin suppresses dexamethasone-induced secretion of plasminogen activator inhibitor-1 in human bone marrow adipocytes. BMC Musculoskelet Disord 2011, 12:82. BioMed Central Full Text
• [17]Magdoud K, Herbepin VG, Touraine R, Almawi WY, Mahjoub T: Plasminogen Activator Inhibitor 1 4G/5G and -844G/A Variants in Idiopathic Recurrent Pregnancy Loss. Am J Reprod Immunol 2013, 70:246-252.
• [18]Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P: Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res 2001, 386:19-33.
• [19]Ferrari P, Schroeder V, Anderson S, Kocovic L, Vogt B, Schiesser D, Marti HP, Ganz R, Frey FJ, Kohler HP: Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients. Transpl 2002, 74:1147-1152.
• [20]Kim H, Cho C, Cho Y, Cho S, Yoon K, Kim K: Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head. BMC Musculoskelet Disord 2011, 12:160. BioMed Central Full Text
• [21]Asano T, Takahashi KA, Fujioka M, Inoue S, Ueshima K, Hirata T, Okamoto M, Satomi Y, Nishino H, Tanaka T, Hirota Y, Kubo T: Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects. Transpl 2004, 77:220-225.
• [22]Koo KH, Kim R, Kim YS, Ahn IO, Cho SH, Song HR, Park YS, Kim H, Wang GJ: Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol 2002, 21:299-303.
• [23]Mont MA, Jones LC, Hungerford DS: Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Join t Surg(Am) 2006, 88:1117-1132.
• [24]Oinuma K, Harada Y, Nawata Y, Takabayashi K, Abe I, Kamikawa K, Moriya H: Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Ann Rheum Dis 2001, 60:1145-1148.
• [25]Sun Y, Feng Y, Zhang C: The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head. Joint Bone Spine 2009, 76:685-690.
• [26]Yang XY, Xu DH: MDR1(ABCB1) gene polymorphisms associated with steroid-induced osteonecrosis of femoral head in systemic lupus erythematosus. Pharm 2007, 62:930-932.
• [27]Kawate K, Yajima H, Sugimoto K, Ono H, Ohmura T, Kobata Y, Murata K, Shigematsu K, Kawamura K, Kawahara I, Maegawa N, Tamai K, Takakura Y, Tamai S: Indications for free vascularized fibular grafting for the treatment of osteonecrosis of the femoral head. BMC Musculoskelet Disord 2007, 8:78. BioMed Central Full Text
• [28]Kenny S, Steele I, Lyons S, Moore AR, Murugesan SV, Tiszlavicz L, Dimaline R, Pritchard DM, Varro A, Dockray GJ: The role of plasminogen activator inhibitor (PAI)-1 in gastric mucosal protection. Am J Physiol Gastrointest Liver Physiol 2013, 304:G814-G822.
• [29]Ichimura A, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou FF: Vaughan DE, van Ypersele de Strihou C, Miyata T: A Small Molecule Inhibitor to Plasminogen Activator Inhibitor 1 Inhibits Macrophage Migration. Arterioscler Thromb Vasc Biol 2013, 33:935-942.
• [30]Li L, Nie W, Zhou H, Yuan W, Li W, Huang W: Association between plasminogen activator inhibitor-1–675 4G/5G polymorphism and sepsis: a meta-analysis. PLoS One 2013, 8:e54883.
• [31]Fang Y, Zhang L, Zeng Z, Lian Y, Jia Y, Zhu H, Xu Y: Promoter polymorphisms of SERPINE1 are associated with the antidepressant response to depression in Alzheimer's disease. Neurosci Lett 2012, 516:217-220.
• [32]Su S, Chen S, Zhao J, Huang J, Wang X, Chen R, Gu D: Plasminogen activator inhibitor-1 gene: selection of tagging single nucleotide polymorphisms and association with coronary heart disease. Arterioscler Thromb Vasc Biol 2006, 26:948-954.