Abstract
Background
Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation.
Methods
Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated.
Results
A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53–26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045).
Conclusion
For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
MA Mont DS Hungerford (1995) ArticleTitleNon-traumatic avascular necrosis of the femoral head J Bone Joint Surg [Am] 77 459–74 Occurrence Handle1:STN:280:DyaK2M7pslOjsw%3D%3D
T Kubo S Yamazoe N Sugano M Fujioka S Naruse N Yoshimura et al. (1997) ArticleTitleInitial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients Magn Reson Imaging 15 1017–23 10.1016/S0730-725X(97)00159-8 Occurrence Handle10.1016/S0730-725X(97)00159-8 Occurrence Handle1:STN:280:DyaK1c%2FjtVahuw%3D%3D Occurrence Handle9364947
T Asano KA Takahashi M Fujioka S Inoue M Okamoto N Sugioka et al. (2003) ArticleTitleABCB1 C3435T and G2677T/A polymorphism decreased the risk for steroid-induced osteonecrosis of the femoral head after kidney transplantation Pharmacogenetics 13 675–82 10.1097/00008571-200311000-00003 Occurrence Handle10.1097/00008571-200311000-00003 Occurrence Handle1:CAS:528:DC%2BD3sXosVOitb8%3D Occurrence Handle14583680
JP Jones SuffixJr (1985) ArticleTitleFat embolism and osteonecrosis Orthop Clin N Am 16 595–633
Fisher DE. The role of fat embolism in the etiology of corticosteroid-induced avascular necrosis: clinical and experimental results. Clin Orthop 1978;68–80.
A Pulkkinen L Viitanen A Kareinen S Lehto M Laakso (2000) ArticleTitleMspI polymorphism at +83 bp in intron 1 of the human apolipoprotein A1 gene is associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronary heart disease Diabetes Care 23 791–5 10.2337/diacare.23.6.791 Occurrence Handle10.2337/diacare.23.6.791 Occurrence Handle1:CAS:528:DC%2BD3cXnvV2isL4%3D Occurrence Handle10840998
K Miyanishi T Yamamoto T Irisa Y Noguchi Y Sugioka Y Iwamoto (1999) ArticleTitleIncreased level of apolipoprotein B/apolipoprotein A1 ratio as a potential risk for osteonecrosis Ann Rheum Dis 58 514–6 10.1136/ard.58.8.514 Occurrence Handle10.1136/ard.58.8.514 Occurrence Handle1:STN:280:DyaK1MzltVWjtw%3D%3D Occurrence Handle10419872
K Miyanishi T Yamamoto T Irisa A Yamashita S Jingushi Y Noguchi et al. (2001) ArticleTitleA high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio as a potential risk factor for corticosteroid-induced osteonecrosis in rabbits Rheumatology (Oxf) 40 196–201 10.1093/rheumatology/40.2.196 Occurrence Handle10.1093/rheumatology/40.2.196 Occurrence Handle1:CAS:528:DC%2BD3MXisFOlt7o%3D
M Scartezini MA Zago EA Chautard-Freire-Maia A Pazin-Filho JA Marin-Neto JK Hotta et al. (2003) ArticleTitleThe X−X−/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample Braz J Med Biol Res 36 369–75 10.1590/S0100-879X2003000300012 Occurrence Handle10.1590/S0100-879X2003000300012 Occurrence Handle1:CAS:528:DC%2BD3sXjs1aksb4%3D Occurrence Handle12640502
A de Padua Mansur J Annicchino-Bizzacchi D Favarato SD Avakian LA Machado Cesar JA Franchini Ramires (2000) ArticleTitleAngiotensin-converting enzyme and apolipoprotein B polymorphisms in coronary artery disease Am J Cardiol 85 1089–93 10.1016/S0002-9149(00)00701-3 Occurrence Handle10.1016/S0002-9149(00)00701-3 Occurrence Handle1:CAS:528:DC%2BD3cXislaqsb8%3D Occurrence Handle10781757
PS Hansen IC Klausen L Lemming LU Gerdes N Gregersen O Faergeman (1994) ArticleTitleApolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex Clin Genet 45 78–83 Occurrence Handle1:STN:280:DyaK2c3ntlehuw%3D%3D Occurrence Handle8004802 Occurrence Handle10.1111/j.1399-0004.1994.tb03998.x
DLS Rios AF Vargas MR Torres AJ Zago SM Callegari-Jacques MH Hutz (2003) ArticleTitleInteraction between SREBP-1a and APOB polymorphisms influences total and low-density lipoprotein cholesterol levels in patients with coronary artery disease Clin Genet 63 380–5 10.1034/j.1399-0004.2003.00057.x Occurrence Handle10.1034/j.1399-0004.2003.00057.x Occurrence Handle1:STN:280:DC%2BD3s3ksFOitw%3D%3D Occurrence Handle12752570
E Verduci C Agostoni ML Biondi G Radaelli M Giovannini E Riva (2004) ArticleTitleApolipoprotein B gene polymorphism and plasma lipid levels in phenylketonuric children Prostaglandins Leukot Essent Fatty Acids 71 117–20 10.1016/j.plefa.2003.12.022 Occurrence Handle10.1016/j.plefa.2003.12.022 Occurrence Handle1:CAS:528:DC%2BD2cXltVCis7o%3D Occurrence Handle15207528
K Shioji T Mannami Y Kokubo Y Goto H Nonogi N Iwai (2004) ArticleTitleAn association analysis between ApoA1 polymorphisms and the high-density lipoprotein (HDL) cholesterol level and myocardial infarction (MI) in Japanese J Hum Genet 49 433–9 Occurrence Handle1:CAS:528:DC%2BD2cXntV2ht7c%3D Occurrence Handle15258834
DL Veenstra JH Best J Hornberger SD Sullivan DE Hricik (1999) ArticleTitleIncidence and long-term cost of steroid-related side effects after renal transplantation Am J Kidney Dis 33 829–39 Occurrence Handle10.1016/S0272-6386(99)70414-2 Occurrence Handle1:STN:280:DyaK1M3jtVWmsw%3D%3D Occurrence Handle10213637
N Sugano T Atsumi K Ohzono T Kubo T Hotokebuchi K Takaoka (2002) ArticleTitleThe 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head J Orthop Sci 7 601–5 10.1007/s007760200108 Occurrence Handle10.1007/s007760200108 Occurrence Handle12355139
SM Boekholdt RJG Peters K Fountoulaki JJP Kastelein EJG Sijbrands (2003) ArticleTitleMolecular variation at the apolipoprotein B gene locus in relation to lipids and cardiovascular disease: a systematic meta-analysis Hum Genet 113 417–25 10.1007/s00439-003-0988-3 Occurrence Handle10.1007/s00439-003-0988-3 Occurrence Handle1:CAS:528:DC%2BD3sXnt1Shtr4%3D Occurrence Handle12942366
ZY Jiang TQ Han GJ Suo DX Feng S Chen XX Cai et al. (2004) ArticleTitlePolymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease World J Gastroenterol 10 1508–12 Occurrence Handle1:CAS:528:DC%2BD2cXns1SisrY%3D Occurrence Handle15133863
KJ Livak (1999) ArticleTitleAllelic discrimination using fluorogenic probes and the 5′ nuclease assay Genet Anal 14 143–9 Occurrence Handle1:CAS:528:DyaK1MXhvVylsbo%3D Occurrence Handle10084106
CJ Glueck R Freiberg T Tracy D Stroop P Wang (1997) ArticleTitleThrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis Clin Orthop 334 43–56 Occurrence Handle9005895
S Saito K Ohzono K Ono (1992) ArticleTitleEarly arteriopathy and postulated pathogenesis of osteonecrosis of the femoral head. The intracapital arterioles Clin Orthop 277 98–110 Occurrence Handle1555362
H Aburatani A Matsumoto H Itoh N Yamada T Murase F Takaku et al. (1988) ArticleTitleA study of DNA polymorphism in the apolipoprotein B gene in a Japanese population Atherosclerosis 72 71–6 10.1016/0021-9150(88)90064-0 Occurrence Handle10.1016/0021-9150(88)90064-0 Occurrence Handle1:CAS:528:DyaL1cXltVGkt78%3D Occurrence Handle2905600
H Iso S Harada T Shimamoto AR Folsom K Koike S Sato et al. (1996) ArticleTitlePolymorphism of the apolipoprotein B gene and blood lipid concentrations in Japanese and Caucasian population samples Atherosclerosis 126 233–41 10.1016/0021-9150(96)05912-6 Occurrence Handle10.1016/0021-9150(96)05912-6 Occurrence Handle1:CAS:528:DyaK28XntVWrsLY%3D Occurrence Handle8902149
H Bai K Saku R Liu S Jimi K Arakawa (1996) ArticleTitleAnalysis of a new polymorphism in the human apolipoprotein A-I gene: association with serum lipoprotein levels and coronary heart disease J Cardiol 28 207–12 Occurrence Handle1:STN:280:DyaK2s%2FovVequg%3D%3D Occurrence Handle8934336
T Demant RS Houlston MJ Caslake JJ Series J Shepherd CJ Packard et al. (1988) ArticleTitleCatabolic rate of low density lipoprotein is influenced by variation in the apolipoprotein B gene J Clin Invest 82 797–802 10.1172/JCI113681 Occurrence Handle10.1172/JCI113681 Occurrence Handle1:CAS:528:DyaL1cXls1Oqtrs%3D Occurrence Handle2901432
AL Boskey CL Raggio PG Bullough JG Kinnett (1983) ArticleTitleChanges in the bone tissue lipids in persons with steroid- and alcohol-induced osteonecrosis Clin Orthop 172 289–95 Occurrence Handle6821997
MM Zaman S Ikemoto N Yoshiike C Date T Yokoyama H Tanaka (1997) ArticleTitleAssociation of apolipoprotein genetic polymorphisms with plasma cholesterol in a Japanese rural population. The Shibata Study Arterioscler Thromb Vasc Biol 17 3495–504 Occurrence Handle1:STN:280:DyaK1c%2FpvFyntg%3D%3D Occurrence Handle9437198
JL Anderson CH Bunker CE Aston MI Kamboh (1997) ArticleTitleRelationship of two apolipoprotein B polymorphisms with serum lipoprotein and lipid levels in African blacks Hum Biol 69 793–807 Occurrence Handle1:STN:280:DyaK1c%2FhsFCkug%3D%3D Occurrence Handle9353975
H Gylling K Kontula TA Miettinen (1995) ArticleTitleCholesterol absorption and metabolism and LDL kinetics in healthy men with different apoprotein E phenotypes and apoprotein B Xba I and LDL receptor Pvu II genotypes Arterioscler Thromb Vasc Biol 15 208–13 Occurrence Handle1:CAS:528:DyaK2MXlt1ektrw%3D Occurrence Handle7749827
Author information
Authors and Affiliations
About this article
Cite this article
Hirata, T., Fujioka, M., Takahashi, K. et al. ApoB C7623T polymorphism predicts risk for steroid-induced osteonecrosis of the femoral head after renal transplantation. J Orthop Sci 12, 199–206 (2007). https://doi.org/10.1007/s00776-007-1110-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00776-007-1110-9