{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:29:06Z","timestamp":1791822546244,"version":"4.3.4"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":141,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,5,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Steroid treatment has become recognized as an important risk factor for avascular osteonecrosis of the femoral head. However, not all patients who receive long-term, high-dose steroids develop osteonecrosis, indicating that there are individual differences in occurrence.<\/jats:p>\n               <jats:p>We explored the relationship between polymorphisms and steroid-induced osteonecrosis of the femoral head (SONFH) incidence with variables. We used a multilevel mixed-effects logistic regression model, which is an expansion of logistic regression, for each type of steroid, primary disease, drug dose, applied duration, and single-nucleotide polymorphism (SNP). We also conducted a dose-response meta-analysis to analyze the cumulative dosage and SONFH risk in mutation carriers. There were significant correlations between the ABCB1 rs1045642 mutant and SONFH in the prednisone-use and methylprednisolone\/prednisone-use populations. The ABCB1 rs2032582 mutant homozygote had a protective effect in the methylprednisolone\/prednisolone renal transplant population. For ApoB rs693, mutation increased the incidence of SONFH in prednisone-use and methylprednisolone\/prednisolone-use populations and renal transplant patients. For ApoB rs1042031, mutation increased the risk of SONFH in the prednisone-use population. The PAI-1 rs1799768 mutation had a protective effect on the SONFH risk prednisone-use and renal transplant populations. ABCB1 rs1045642 mutations have a protective effect against SONFH, and ApoB rs693 and rs1042031 increase the SONFH risk. Cumulative dosage and treatment duration had little effect on the results. In addition, there was a dose-effect correlation in ABCB1 rs1045642 and rs2032582 mutation carriers.<\/jats:p>","DOI":"10.1042\/bsr20190024","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T16:13:57Z","timestamp":1555517637000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Association between genetic polymorphisms and osteonecrosis in steroid treatment populations: a detailed stratified and dose-response meta-analysis"],"prefix":"10.1042","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-0581","authenticated-orcid":false,"given":"Jun","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthopedics & Traumatology, Yuxi Municipal Hospital of TCM, Yunnan Province 653100, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Orthopedics & Traumatology, Yuxi Municipal Hospital of TCM, Yunnan Province 653100, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoge","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics & Traumatology, Yuxi Municipal Hospital of TCM, Yunnan Province 653100, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,5,14]]},"reference":[{"key":"2021111619350174200_B1","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1007\/s00264-018-3994-8","article-title":"The role of autophagy in steroid necrosis of the femoral head: a comprehensive research review","volume":"42","author":"Luo","year":"2018","journal-title":"Int. Orthop."},{"key":"2021111619350174200_B2","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.ocl.2004.03.002","article-title":"Vascular anatomy and microcirculation of skeletal zones vulnerable to osteonecrosis: vascularization of the femoral head","volume":"35","author":"Johnson","year":"2004","journal-title":"Orthop. Clin. North Am."},{"key":"2021111619350174200_B3","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3109\/17453670903025378","article-title":"Incidence of genetic polymorphisms involved in lipid metabolism amongst Chinese patients with osteonecrosis of the femoral head","volume":"80","author":"He","year":"2009","journal-title":"Acta Orthop."},{"key":"2021111619350174200_B4","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.gene.2018.05.091","article-title":"The pathogenesis of steroid-induced osteonecrosis of the femoral head: a systematic review of the literature","volume":"671","author":"Wang","year":"2018","journal-title":"Gene"},{"key":"2021111619350174200_B5","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.steroids.2013.01.004","article-title":"Genetic risk factors for glucocorticoid-induced osteonecrosis: a meta-analysis","volume":"78","author":"Gong","year":"2013","journal-title":"Steroids"},{"key":"2021111619350174200_B6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.gene.2015.03.023","article-title":"Association of ABCB1\/MDR1 polymorphisms in patients with glucocorticoid-induced osteonecrosis of the femoral head: evidence for a meta-analysis","volume":"569","author":"Zhou","year":"2015","journal-title":"Gene"},{"key":"2021111619350174200_B7","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.12659\/MSM.891286","article-title":"ABCB1 gene polymorphisms and glucocorticoid-induced avascular necrosis of the femoral head susceptibility: a meta-analysis","volume":"20","author":"Li","year":"2014","journal-title":"Med. Sci. Monit."},{"key":"2021111619350174200_B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/08941939.2017.1385663","article-title":"Correlation between steroid-induced osteonecrosis of the femoral head and hepatic CYP3A activity: a systematic review and meta-analysis","volume":"2017","author":"Guo","year":"2017","journal-title":"J. Invest. Surg."},{"key":"2021111619350174200_B9","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA"},{"key":"2021111619350174200_B10","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/00001648-199305000-00005","article-title":"Meta-analysis of epidemiologic dose-response data","volume":"4","author":"Berlin","year":"1993","journal-title":"Epidemiology"},{"key":"2021111619350174200_B11","first-page":"3647","article-title":"Efficacy of glucocorticoids in rodents of severe acute pancreatitis: a meta-analysis","volume":"7","author":"Yu","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"2021111619350174200_B12","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","article-title":"Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses","volume":"25","author":"Stang","year":"2010","journal-title":"Eur. J. Epidemiol."},{"key":"2021111619350174200_B13","doi-asserted-by":"publisher","first-page":"e0128201","DOI":"10.1371\/journal.pone.0128201","article-title":"The SNP rs931794 in 15q25.1 is associated with lung cancer risk: a hospital-based case-control study and meta-analysis","volume":"10","author":"Wang","year":"2015","journal-title":"PLoS ONE"},{"key":"2021111619350174200_B14","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1007\/s00198-018-4487-8","article-title":"Sleep duration and the risk of osteoporosis amongst middle-aged and elderly adults: a dose-response meta-analysis","volume":"29","author":"Wang","year":"2018","journal-title":"Osteoporos. Int."},{"key":"2021111619350174200_B15","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1177\/1536867X0600600103","article-title":"Generalized least squares for trend estimation of summarized dose\u2013response data","volume":"6","author":"Orsini","year":"2006","journal-title":"Stata J."},{"key":"2021111619350174200_B16","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1089\/gtmb.2016.0260","article-title":"Polymorphisms in the glucocorticoid receptor gene and associations with glucocorticoid-induced avascular osteonecrosis of the femoral head","volume":"21","author":"Zhao","year":"2017","journal-title":"Genet. Test Mol. Biomarkers"},{"key":"2021111619350174200_B17","first-page":"A94","article-title":"Influence of BCL2L11 polymorphism on osteonecrosis during treatment of childhood acute lymphoblastic leukemia","volume":"14","author":"Plesa","year":"2017","journal-title":"Pharmacogenomics J."},{"key":"2021111619350174200_B18","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1182\/blood-2015-05-643601","article-title":"Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia","volume":"126","author":"Karol","year":"2015","journal-title":"Blood"},{"key":"2021111619350174200_B19","first-page":"1364","article-title":"The correlation between apolipoprotein gene polymorphisms and steroid-induced osteonecrosis of the femoral head","volume":"36","author":"Wei","year":"2015","journal-title":"Guangdong Med. J."},{"key":"2021111619350174200_B20","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.1007\/s11033-014-3173-y","article-title":"Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-induced osteonecrosis of the femoral head in Chinese population","volume":"41","author":"Zhang","year":"2014","journal-title":"Mol. Biol. Rep."},{"key":"2021111619350174200_B21","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1089\/gtmb.2013.0374","article-title":"MDR1 gene polymorphisms are associated with glucocorticoid-induced avascular necrosis of the femoral head in a Chinese population","volume":"18","author":"Xue","year":"2014","journal-title":"Genet. Test Mol. Biomarkers"},{"key":"2021111619350174200_B22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s13000-014-0229-1","article-title":"Association of apolipoprotein A5 genetic polymorphisms with steroid-induced osteonecrosis of femoral head in a Chinese Han population","volume":"9","author":"Cui","year":"2014","journal-title":"Diagn. Pathol."},{"key":"2021111619350174200_B23","first-page":"1","article-title":"Relationship between apolipoprotein B gene polymorphism and tendon-vessel stagnation syndrome of steroid induced osteonecrosis of the femoral head","volume":"54","author":"Zeng","year":"2014","journal-title":"Shandong Med. J."},{"key":"2021111619350174200_B24","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/1746-1596-8-169","article-title":"Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population","volume":"8","author":"Zhang","year":"2013","journal-title":"Diagn Pathol."},{"key":"2021111619350174200_B25","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/1746-1596-8-186","article-title":"Association of a polymorphism in PON-1 gene with steroid-induced osteonecrosis of femoral head in Chinese Han population","volume":"8","author":"Wang","year":"2013","journal-title":"Diagn. Pathol."},{"key":"2021111619350174200_B26","first-page":"87","article-title":"Association between polymorphisms of steroid induced osteonecrosis of the femoral head and traditional Chinese medicine syndrome types","volume":"44","author":"Li","year":"2012","journal-title":"J. New Chin. Med."},{"key":"2021111619350174200_B27","first-page":"321","article-title":"Relationship between gene polymorphisms and syndrome types in steroid- induced femoral head osteonecrosis","volume":"33","author":"Wei","year":"2011","journal-title":"J. Shandong Med. College"},{"key":"2021111619350174200_B28","first-page":"7403","article-title":"Relationship between gene polymorphisms and hereditary susceptibility of steroid-induced femoral head osteonecrosis in Linyi City of Shandong Province","volume":"15","author":"Wei","year":"2011","journal-title":"J. Clin. Rehabilitative Tissue Eng. Res."},{"key":"2021111619350174200_B29","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.1182\/blood-2011-05-355206","article-title":"Polymorphism in the PAI-1 (SERPINE1) gene and the risk of osteonecrosis in children with acute lymphoblastic leukemia","volume":"118","author":"Bond","year":"2011","journal-title":"Blood"},{"key":"2021111619350174200_B30","doi-asserted-by":"publisher","first-page":"325","DOI":"10.3109\/17453670903025378","article-title":"Incidence of genetic polymorphisms involved in lipid metabolism amongst Chinese patients with osteonecrosis of the femoral head","volume":"80","author":"He","year":"2009","journal-title":"Acta Orthop."},{"key":"2021111619350174200_B31","first-page":"284","article-title":"Genetic susceptibility of corticosteroid-induced osteonecrosis of femoral head","volume":"2","author":"He","year":"2009","journal-title":"Chin. Bone Joint Surg."},{"key":"2021111619350174200_B32","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1007\/s00776-008-1244-4","article-title":"Combination analysis of three polymorphisms for predicting the risk for steroid-induced osteonecrosis of the femoral head","volume":"13","author":"Kuribayashi","year":"2008","journal-title":"J. Orthop. Sci."},{"key":"2021111619350174200_B33","doi-asserted-by":"publisher","first-page":"4496","DOI":"10.1182\/blood-2007-11-123885","article-title":"A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children\u2019s Oncology Group","volume":"111","author":"French","year":"2008","journal-title":"Blood"},{"key":"2021111619350174200_B34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/1471-2334-8-27","article-title":"Roles of TNF-alpha gene polymorphisms in the occurrence and progress of SARS-Cov infection: a case-control study","volume":"8","author":"Wang","year":"2008","journal-title":"BMC Infect. Dis."},{"key":"2021111619350174200_B35","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1007\/s00774-007-0770-z","article-title":"Genetic association of a polymorphism of the cAMP-responsive element binding protein-binding protein with steroid-induced osteonecrosis after kidney transplantation","volume":"25","author":"Tamura","year":"2007","journal-title":"J. Bone Miner. Metab."},{"key":"2021111619350174200_B36","first-page":"930","article-title":"MDR1(ABCB1) gene polymorphisms associated with steroid-induced osteonecrosis of femoral head in systemic lupus erythematosus","volume":"62","author":"Yang","year":"2007","journal-title":"Pharmazie"},{"key":"2021111619350174200_B37","first-page":"516","article-title":"Low molecular weight phenotype of Apo(a) is a risk factor of corticosteroid-induced osteonecrosis of the femoral head after renal transplant","volume":"34","author":"Hirata","year":"2007","journal-title":"J. Rheumatol."},{"key":"2021111619350174200_B38","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00776-007-1110-9","article-title":"ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation","volume":"12","author":"Hirata","year":"2007","journal-title":"J. Orthop. Sci."},{"key":"2021111619350174200_B39","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1093\/ndt\/gfl400","article-title":"Thrombophilia and avascular necrosis of femoral head in kidney allograft recipients","volume":"21","author":"Ekmekci","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021111619350174200_B40","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.transproceed.2005.12.062","article-title":"Association of corticosteroids and factor V, prothrombin, and MTHFR gene mutations with avascular osteonecrosis in renal allograft recipients","volume":"38","author":"Celik","year":"2006","journal-title":"Transplant. Proc."},{"key":"2021111619350174200_B41","doi-asserted-by":"publisher","first-page":"3930","DOI":"10.1200\/JCO.2004.11.020","article-title":"Pharmacogenetic risk factors for osteonecrosis of the hip amongst children with leukemia","volume":"22","author":"Relling","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"2021111619350174200_B42","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1097\/01.TP.0000101433.99651.96","article-title":"Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects","volume":"77","author":"Asano","year":"2004","journal-title":"Transplantation"},{"key":"2021111619350174200_B43","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s10776-003-0646-7","article-title":"Genetic analysis of steroid-induced osteonecrosis of the femoral head","volume":"8","author":"Asano","year":"2003","journal-title":"J. Orthop. Sci."},{"key":"2021111619350174200_B44","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1097\/00008571-200311000-00003","article-title":"ABCB1 C3435T and G2677T\/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation","volume":"13","author":"Asano","year":"2003","journal-title":"Pharmacogenetics"},{"key":"2021111619350174200_B45","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1097\/00007890-200210270-00016","article-title":"Association of plasminogen activator inhibitor-1 genotype with avascular osteonecrosis in steroid-treated renal allograft recipients","volume":"74","author":"Ferrari","year":"2002","journal-title":"Transplantation"},{"key":"2021111619350174200_B46","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.3389\/fphys.2018.01684","article-title":"Lipid transporter activity-related genetic polymorphisms are associated with steroid-induced osteonecrosis of the femoral head: an updated meta-analysis based on the GRADE guidelines","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Physiol."},{"key":"2021111619350174200_B47","doi-asserted-by":"publisher","first-page":"13688","DOI":"10.4238\/2015.October.28.31","article-title":"VEGF, eNOS, and ABCB1 genetic polymorphisms may increase the risk of osteonecrosis of the femoral head","volume":"14","author":"Zhou","year":"2015","journal-title":"Genet. Mol. Res."},{"key":"2021111619350174200_B48","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.2106\/00004623-199409000-00014","article-title":"Avascular necrosis of bone after cardiac transplantation. Prevalence and relationship to administration and dosage of steroids","volume":"76","author":"Bradbury","year":"1994","journal-title":"J. Bone Joint Surg. Am."},{"key":"2021111619350174200_B49","doi-asserted-by":"publisher","first-page":"2060","DOI":"10.1093\/ndt\/gfy148","article-title":"Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study","volume":"33","author":"Schachtner","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"2021111619350174200_B50","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1007\/s10753-014-9917-y","article-title":"The risk factors of avascular necrosis in patients with systemic lupus erythematosus: a meta-analysis","volume":"37","author":"Zhu","year":"2014","journal-title":"Inflammation"},{"key":"2021111619350174200_B51","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1007\/s00198-016-3824-z","article-title":"Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis","volume":"28","author":"Zhao","year":"2017","journal-title":"Osteoporos. Int."}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20190024\/847659\/bsr-2019-0024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20190024\/847659\/bsr-2019-0024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:24:46Z","timestamp":1637094286000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/39\/5\/BSR20190024\/219118\/Association-between-genetic-polymorphisms-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5,31]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20190024","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5]]},"published":{"date-parts":[[2019,5]]},"article-number":"BSR20190024"}}