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Published in: Diagnostic Pathology 1/2013

Open Access 01-12-2013 | Research

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

Authors: Yanqiong Zhang, Rongtian Wang, Shangzhu Li, Xiangying Kong, Zhiyao Wang, Weiheng Chen, Na Lin

Published in: Diagnostic Pathology | Issue 1/2013

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Abstract

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.

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Literature
1.
go back to reference 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. 10.1155/2011/196021.PubMedCentralCrossRefPubMed 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. 10.1155/2011/196021.PubMedCentralCrossRefPubMed
2.
go back to reference 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. 10.1007/s11999-008-0147-1.PubMedCentralCrossRefPubMed 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. 10.1007/s11999-008-0147-1.PubMedCentralCrossRefPubMed
3.
go back to reference 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. 10.1007/s10776-003-0646-7.CrossRefPubMed 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. 10.1007/s10776-003-0646-7.CrossRefPubMed
4.
go back to reference 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: 78-10.1186/1746-1596-7-78.PubMedCentralCrossRefPubMed 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: 78-10.1186/1746-1596-7-78.PubMedCentralCrossRefPubMed
5.
go back to reference 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: 62-10.1186/1746-1596-5-62.PubMedCentralCrossRefPubMed 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: 62-10.1186/1746-1596-5-62.PubMedCentralCrossRefPubMed
6.
go back to reference 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. 10.1007/s00776-008-1244-4.CrossRefPubMed 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. 10.1007/s00776-008-1244-4.CrossRefPubMed
7.
go back to reference 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. 10.1002/jor.21492.CrossRefPubMed 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. 10.1002/jor.21492.CrossRefPubMed
8.
go back to reference 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. 10.1007/s00774-007-0770-z.CrossRefPubMed 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. 10.1007/s00774-007-0770-z.CrossRefPubMed
9.
go back to reference Guan XY, Han D: Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci. 2010, 15: 365-370. 10.1007/s00776-010-1452-6.CrossRefPubMed Guan XY, Han D: Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits. J Orthop Sci. 2010, 15: 365-370. 10.1007/s00776-010-1452-6.CrossRefPubMed
10.
go back to reference 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. 10.1177/147323001003800333.CrossRefPubMed 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. 10.1177/147323001003800333.CrossRefPubMed
11.
go back to reference Fortenberry YM: Plasminogen activator inhibitor-1 inhibitors: a patent review (2006 - present). Expert Opin Ther Pat. 2013, 23: 801-815. 10.1517/13543776.2013.782393.CrossRefPubMed Fortenberry YM: Plasminogen activator inhibitor-1 inhibitors: a patent review (2006 - present). Expert Opin Ther Pat. 2013, 23: 801-815. 10.1517/13543776.2013.782393.CrossRefPubMed
12.
go back to reference 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. 10.1007/s00296-013-2717-0.CrossRefPubMed 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. 10.1007/s00296-013-2717-0.CrossRefPubMed
13.
go back to reference Declerck PJ, Gils A: Three decades of research on plasminogen activator inhibitor-1: a multifaceted serpin. Semin Thromb Hemost. 2013, 39: 356-364. 10.1055/s-0033-1334487.CrossRefPubMed Declerck PJ, Gils A: Three decades of research on plasminogen activator inhibitor-1: a multifaceted serpin. Semin Thromb Hemost. 2013, 39: 356-364. 10.1055/s-0033-1334487.CrossRefPubMed
14.
go back to reference 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. 10.1016/j.trsl.2006.05.001.CrossRefPubMed 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. 10.1016/j.trsl.2006.05.001.CrossRefPubMed
15.
go back to reference 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. 10.2220/biomedres.31.281.CrossRefPubMed 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. 10.2220/biomedres.31.281.CrossRefPubMed
16.
go back to reference 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: 82-10.1186/1471-2474-12-82.PubMedCentralCrossRefPubMed 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: 82-10.1186/1471-2474-12-82.PubMedCentralCrossRefPubMed
17.
go back to reference 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. 10.1111/aji.12116.CrossRefPubMed 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. 10.1111/aji.12116.CrossRefPubMed
18.
go back to reference Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P: Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res. 2001, 386: 19-33.CrossRefPubMed Glueck CJ, Freiberg RA, Fontaine RN, Tracy T, Wang P: Hypofibrinolysis, thrombophilia, osteonecrosis. Clin Orthop Relat Res. 2001, 386: 19-33.CrossRefPubMed
19.
go back to reference 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. 10.1097/00007890-200210270-00016.CrossRef 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. 10.1097/00007890-200210270-00016.CrossRef
20.
go back to reference 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: 160-10.1186/1471-2474-12-160.PubMedCentralCrossRefPubMed 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: 160-10.1186/1471-2474-12-160.PubMedCentralCrossRefPubMed
21.
go back to reference 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. 10.1097/01.TP.0000101433.99651.96.CrossRef 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. 10.1097/01.TP.0000101433.99651.96.CrossRef
22.
go back to reference 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. 10.1007/s100670200078.CrossRefPubMed 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. 10.1007/s100670200078.CrossRefPubMed
23.
go back to reference 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.CrossRef 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.CrossRef
24.
go back to reference 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. 10.1136/ard.60.12.1145.PubMedCentralCrossRefPubMed 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. 10.1136/ard.60.12.1145.PubMedCentralCrossRefPubMed
25.
go back to reference 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. 10.1016/j.jbspin.2009.04.002.CrossRefPubMed 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. 10.1016/j.jbspin.2009.04.002.CrossRefPubMed
26.
go back to reference 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. 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.
go back to reference 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: 78-10.1186/1471-2474-8-78.PubMedCentralCrossRefPubMed 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: 78-10.1186/1471-2474-8-78.PubMedCentralCrossRefPubMed
28.
go back to reference 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. 10.1152/ajpgi.00017.2013.PubMedCentralCrossRefPubMed 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. 10.1152/ajpgi.00017.2013.PubMedCentralCrossRefPubMed
29.
go back to reference 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. 10.1161/ATVBAHA.113.301224.CrossRefPubMed 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. 10.1161/ATVBAHA.113.301224.CrossRefPubMed
30.
go back to reference 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: e54883-10.1371/journal.pone.0054883.PubMedCentralCrossRefPubMed 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: e54883-10.1371/journal.pone.0054883.PubMedCentralCrossRefPubMed
31.
go back to reference 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. 10.1016/j.neulet.2012.03.090.CrossRefPubMed 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. 10.1016/j.neulet.2012.03.090.CrossRefPubMed
32.
go back to reference 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. 10.1161/01.ATV.0000204731.17646.f2.CrossRefPubMed 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. 10.1161/01.ATV.0000204731.17646.f2.CrossRefPubMed
Metadata
Title
Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population
Authors
Yanqiong Zhang
Rongtian Wang
Shangzhu Li
Xiangying Kong
Zhiyao Wang
Weiheng Chen
Na Lin
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2013
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-8-169

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