Skip to main content
SpringerLink
Log in

Genetic polymorphisms in IL1B predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese Han population

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The purpose of this research was to examine if the IL1B gene polymorphism has impact on the risk of steroid-induced ONFH in Chinese population. We found that IL1B rs1143630 decreased the SANFH’s risk and IL1B rs2853550 increased the risk of steroid-induced ONFH. So, we guess that IL1B gene influences the genetic susceptibility of steroid-induced ONFH.

Introduction

Genetic polymorphisms in IL1B gene could be related in the pathogenesis of osteonecrosis. Discusses on the relationship between the IL1B gene and steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is still less in Chinese Han population. So, in this research, we want to examine whether the IL1B gene polymorphism has impact on the risk of steroid-induced ONFH in Chinese population.

Methods

A total of 286 steroid-induced ONFH patients and 441 controls were recruited, and seven SNPs (rs2853550, rs1143643, rs3136558, rs1143630, rs1143627, rs16944, and rs1143623) in IL1B gene were selected; unconditional logistic regression analysis was used to research the influence on the risk of steroid-induced ONFH. Functional annotations of IL1B variants were performed by RegulomeDB and HaploReg.

Results

rs1143630 (A>C) in the IL1B gene decreased the risk of steroid-induced ONFH in the allele model (OR = 0.69, 95%CI 0.51–0.93, p = 0.014). Further genetic model analyses found that IL1B rs2853550 AG genotype increased the risk of steroid-induced ONFH compared with the people who are carriers of the IL1B rs2853550 GG genotype (OR = 1.69, 95%CI 1.16–2.46, p = 0.012). In the dominant model, IL1B rs1143630 GG-GT genotype decreased the risk of steroid-induced ONFH (OR = 0.62, 95%CI 0.44–0.87, p = 0.0051). And further haplotype analysis was performed, while the result was not significant. Using RegulomeDB and HaploReg, rs2853550 is likely to affect TF binding, any motif and DNase peak.

Conclusions

We guess that IL1B gene influences the genetic susceptibility of steroid-induced ONFH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Aaron RK (1998) Importance of the early diagnosis of hip pain: new approaches to hip preservation in osteonecrosis. Med Health Rhode Island 81(5):157–161

    CAS  Google Scholar 

  2. Zalavras CG, Vartholomatos G, Dokou E, Malizos KN (2004) Genetic background of osteonecrosis: associated with thrombophilic mutations? Clin Orthop Relat Res 422:251–255

    Article  Google Scholar 

  3. Mont MA, Hungerford DS (1995) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am Vol 77(3):459–474

    Article  CAS  Google Scholar 

  4. Lavernia CJ, Sierra RJ, Grieco FR (1999) Osteonecrosis of the femoral head. J Am Acad Orthop Surg 7(4):250–261

    Article  CAS  PubMed  Google Scholar 

  5. Mont MA, Jones LC, Hungerford DS (2006) Nontraumatic osteonecrosis of the femoral head: ten years later. The Journal of bone and joint surgery American 88(5):1117–1132. https://doi.org/10.2106/JBJS.E.01041

    Article  Google Scholar 

  6. Hirota Y, Hirohata T, Fukuda K, Mori M, Yanagawa H, Ohno Y, Sugioka Y (1993) Association of alcohol intake, cigarette smoking, and occupational status with the risk of idiopathic osteonecrosis of the femoral head. Am J Epidemiol 137(5):530–538

    Article  CAS  PubMed  Google Scholar 

  7. Brown ME, Hickling P, Wilkin TJ (2001) Postpartum multifocal avascular necrosis: what are the possible etiologies? J Clin Rheumatol 7(1):38–41

    Article  CAS  PubMed  Google Scholar 

  8. Du J, Jin T, Cao Y, Chen J, Guo Y, Sun M, Li J, Zhang X, Wang G, Wang J (2016) Association between genetic polymorphisms of MMP8 and the risk of steroid-induced osteonecrosis of the femoral head in the population of northern China. Medicine 95(37):e4794. https://doi.org/10.1097/md.0000000000004794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Li Y, Wang Y, Guo Y, Wang Q, Ouyang Y, Cao Y, Jin T, Wang J (2016) OPG and RANKL polymorphisms are associated with alcohol-induced osteonecrosis of the femoral head in the north area of China population in men. Medicine 95(25):e3981. https://doi.org/10.1097/MD.0000000000003981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Su B, Yu Y, Yang H, Ouyang Y, Feng T, Jin T, Zhao H (2016) Nitric oxide of genetic variants is associated with alcohol-induced osteonecrosis risk of the femoral head in a Han population. Int J Clin Exp Pathol

  11. Bird S, Zou J, Wang T, Munday B, Cunningham C, Secombes CJ (2002) Evolution of interleukin-1beta. Cytokine Growth Factor Rev 13(6):483–502

    Article  CAS  PubMed  Google Scholar 

  12. Dinarello CA (2002) The IL-1 family and inflammatory diseases. Clin Exp Rheumatol 20(5 Suppl 27):S1–S13

  13. Li C, Wang C (2013) Current evidences on IL1B polymorphisms and lung cancer susceptibility: a meta-analysis. Tumour Biol 34(6):3477–3482. https://doi.org/10.1007/s13277-013-0925-6

    Article  CAS  PubMed  Google Scholar 

  14. Meulenbelt I, Seymour AB, Nieuwland M, Huizinga TW, van Duijn CM, Slagboom PE (2004) Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip. Arthritis Rheum 50(4):1179–1186. https://doi.org/10.1002/art.20121

    Article  CAS  PubMed  Google Scholar 

  15. Timms AE, Crane AM, Sims AM, Cordell HJ, Bradbury LA, Abbott A, Coyne MR, Beynon O, Herzberg I, Duff GW, Calin A, Cardon LR, Wordsworth BP, Brown MA (2004) The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis. Am J Hum Genet 75(4):587–595. https://doi.org/10.1086/424695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li L, Shi B, Zheng W, Xing W, Zhao Y, Li F, Xin D, Jin T, Zhu Y, Yang X (2017) Association of IL-1A and IL-1B polymorphisms with ankylosing spondylitis among the Chinese Han population: a case-control study. Oncotarget 8(17):28278–28284

    PubMed  PubMed Central  Google Scholar 

  17. Samara S, Kollia P, Dailiana Z, Chassanidis C, Papatheodorou L, Koromila T, Malizos KN (2012) Predictive role of cytokine gene polymorphisms for the development of femoral head osteonecrosis. Dis Markers 33(4):215–221. https://doi.org/10.3233/DMA-2012-0928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Totty WG, Murphy WA, Ganz WI, Kumar B, Daum WJ, Siegel BA (1984) Magnetic resonance imaging of the normal and ischemic femoral head. AJR Am J Roentgenol 143(6):1273–1280. https://doi.org/10.2214/ajr.143.6.1273

    Article  CAS  PubMed  Google Scholar 

  19. Koo KH, Kim R, Kim YS, Ahn IO, Cho SH, Song HR, Park YS, Kim H, Wang GJ (2002) Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol 21(4):299–303. https://doi.org/10.1007/s100670200078

    Article  PubMed  Google Scholar 

  20. Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. Current protocols in human genetics Chapter 2:Unit 2.12. https://doi.org/10.1002/0471142905.hg0212s60

  21. Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T, Lin WM, Wang M, Feng W, Zander T, MacConaill L, Lee JC, Nicoletti R, Hatton C, Goyette M, Girard L, Majmudar K, Ziaugra L, Wong KK, Gabriel S, Beroukhim R, Peyton M, Barretina J, Dutt A, Emery C, Greulich H, Shah K, Sasaki H, Gazdar A, Minna J, Armstrong SA, Mellinghoff IK, Hodi FS, Dranoff G, Mischel PS, Cloughesy TF, Nelson SF, Liau LM, Mertz K, Rubin MA, Moch H, Loda M, Catalona W, Fletcher J, Signoretti S, Kaye F, Anderson KC, Demetri GD, Dummer R, Wagner S, Herlyn M, Sellers WR, Meyerson M, Garraway LA (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39(3):347–351. https://doi.org/10.1038/ng1975

    Article  CAS  PubMed  Google Scholar 

  22. Adamec C (1964) Example of the use of the nonparametric test. Test X2 for comparison of 2 independent examples. Ceskoslovenske zdravotnictvi 12:613–619

    CAS  PubMed  Google Scholar 

  23. Bland JM, Altman DG (2000) Statistics notes. The odds ratio. BMJ 320(7247):1468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dupont WD, Plummer WD Jr (1998) Power and sample size calculations for studies involving linear regression. Control Clin Trials 19(6):589–601

    Article  CAS  PubMed  Google Scholar 

  25. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2):263–265. https://doi.org/10.1093/bioinformatics/bth457

    Article  CAS  Google Scholar 

  26. Hawley ME, Kidd KK (1995) HAPLO: a program using the EM algorithm to estimate the frequencies of multi-site haplotypes. J Hered 86(5):409–411

    Article  CAS  PubMed  Google Scholar 

  27. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S, Cherry JM, Snyder M (2012) Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 22(9):1790–1797. https://doi.org/10.1101/gr.137323.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ward LD, Kellis M (2016) HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res 44(D1):D877–D881. https://doi.org/10.1093/nar/gkv1340

    Article  CAS  PubMed  Google Scholar 

  29. Balkwill F (1997) Cytokine amplification and inhibition of immune and inflammatory responses. J Viral Hepat 4(Suppl 2):6–15

    Article  PubMed  Google Scholar 

  30. Witkin SS, Gerber S, Ledger WJ (2002) Influence of interleukin-1 receptor antagonist gene polymorphism on disease. Clin Infect Dis 34(2):204–209. https://doi.org/10.1086/338261

    Article  CAS  PubMed  Google Scholar 

  31. Lukens JR, Gross JM, Calabrese C, Iwakura Y, Lamkanfi M, Vogel P, Kanneganti TD (2014) Critical role for inflammasome-independent IL-1beta production in osteomyelitis. Proc Natl Acad Sci U S A 111(3):1066–1071. https://doi.org/10.1073/pnas.1318688111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF Jr, Rabkin CS (2000) Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404(6776):398–402. https://doi.org/10.1038/35006081

    Article  CAS  PubMed  Google Scholar 

  33. Hwang IR, Kodama T, Kikuchi S, Sakai K, Peterson LE, Graham DY, Yamaoka Y (2002) Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection. Gastroenterology 123(6):1793–1803. https://doi.org/10.1053/gast.2002.37043

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to all the patients and individuals in the study who made this work possible. We would also like to thank the clinicians and hospital staffs who contributed to data collection for this study.

Funding

This work was supported by the Shaanxi Science and Technology Development Plan Project (Grant Nos. 2013K12-17-03 and 2015SF025).

Author information

Authors and Affiliations

  1. Department of Clinical Laboratory, HongHui Affiliated Hospital of Xi’an Jiaotong University College of Medicine, Xi’an, 710054, Shaanxi, China

    Y. Yu

  2. Department of Orthopedics, Suizhou Hospital, Hubei University Of Medicine, Suizhou, 441300, Hubei, China

    Y. Zhang

  3. Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, School of Life Sciences, Northwest University, Xi’an, 710069, Shaanxi, China

    J. Wu, Y. Sun, Z. Xiong, F. Niu, L. Lei, S. Du & P. Chen

  4. Department of Osteonecrosis and Joint Reconstruction Ward, HongHui Affiliated Hospital of Xi’an Jiaotong University College of Medicine, #555 Youyi East Road, Xi’an, 710054, Shaanxi, China

    Z. Yang

Authors
  1. Y. Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Z. Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. Niu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. Lei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. P. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Z. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z. Yang.

Ethics declarations

Our present study strictly followed the principles of the Declaration of Helsinki of the World Medical Association and was approved by the Ethics Committee of Zhengzhou Traditional Chinese Medicine Traumatology Hospital and HongHui Affiliated Hospital of Xi’an Jiaotong University College of Medicine. Informed consent forms were signed by all participants.

Conflict of interest

Yan Yu, Yiming Zhang, Jiamin Wu, Yao Sun, Zichao Xiong, Fanglin Niu, Lingyu Lei, Shuli Du, Peng Chen, and Zhi Yang declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yan Yu and Yiming Zhang joint first authors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yu, Y., Zhang, Y., Wu, J. et al. Genetic polymorphisms in IL1B predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese Han population. Osteoporos Int 30, 871–877 (2019). https://doi.org/10.1007/s00198-019-04835-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-019-04835-9

Keywords

Search

Navigation