Skip to main content

Advertisement

SpringerLink
Log in

Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: a meta-analysis

  • Original Article
  • Published:
Modern Rheumatology

Abstract

Objectives

Many publications have evaluated the correlation between HLA-B27 polymorphisms and ankylosing spondylitis (AS), with conflicting results. We carried out this new meta-analysis in order to collect all the relevant studies to further clarify the association of HLA-B27 polymorphisms with AS susceptibility.

Methods

Relevant published data were retrieved through Medline, PubMed, Web of Science, CNKI, and the Chinese BioMedical Literature Database on disc. The statistical analysis was conducted using Review Manager Version 5.0 and STATA 11.0. From these data, the odds ratio (OR) with a 95 % confidence interval (95 % CI) was calculated.

Results

(1) A total of 38 studies, including 3,410 AS cases and 1,735 healthy controls, were collected in this meta-analysis. (2) Our results showed that B2704 was a risk factor but B2703, B2706, B2707, B2727, B2729, and B2747 may be protective factors for AS worldwide. (3) These subtypes, such as B2701, B2702, B2705, B2708–15, B2717–20, B2723–24, B2733, B2735, B2740, B2746, B2749, and B2767, showed no association with susceptibility to AS. There was a huge difference with previous reports for B2702 and B2705. (4) The B2702, B2704 and B2705 subtypes have existed high heterogeneity but no publication bias.

Conclusions

This meta-analysis in our study suggested that B2704 might be a potential risk factor, however, B2703, B2706, and B2707 might be potential protective factors of AS, especially in Asia.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379–90.

    Article  PubMed  Google Scholar 

  2. Ng SC, et al. Epidemiology of spondyloarthritis in the People’s Republic of China: review of the literature and commentary. Semin Arthritis Rheum. 2007;37:39–47.

    Article  PubMed  Google Scholar 

  3. Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum. 1997;40:1823–8.

    Article  PubMed  CAS  Google Scholar 

  4. Braun J, Bollow M, Remlinger G, Eggens U, Rudwaleit M, Distler A, Sieper J. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum. 1998;41:58–67.

    Article  PubMed  CAS  Google Scholar 

  5. Végvári A, Szabó Z, Szántó S, Glant TT, Mikecz K, Szekanecz Z. The genetic background of ankylosing spondylitis. Joint Bone Spine. 2009;76:623–8.

    Article  PubMed  Google Scholar 

  6. Kaas Q, Ruiz M, Lefranc MP. IMGT/3Dstructure-DB and IMGT/Structural Query, a database and a tool for immunoglobulin, T cell receptor and MHC structural data. Nucleic Acids Res. 2004;32:D208–10.

    Article  PubMed  CAS  Google Scholar 

  7. Park K-S, Kang S-Y, Lee W-I. HLA-B27 subtypes in Korean patients with ankylosing spondylitis. Korean J Lab Med. 2008;28:46–52.

    Article  PubMed  CAS  Google Scholar 

  8. Radhia KB, Ayed-Jendoubi S, Sfar I, Romdhane TB, Makhlouf M, Gorgi Y, Ayed K. Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis. Joint Bone Spine. 2008;75:172–5.

    Article  PubMed  Google Scholar 

  9. Pazár B, Sáfrány E, Gergely P, Szántó S, Szekanecz Z, Poór G. Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype in Hungarian patients with ankylosing spondylitis. J Rheumatol. 2010;37:379–84.

    Article  PubMed  Google Scholar 

  10. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum. 1984;27:361–8.

    Article  PubMed  Google Scholar 

  11. Chou CT, Chen JM, Hsu CM, Chen SJ. HLA-B27 and its subtypes in 4 Taiwanese aborigine tribes: a comparison to Han Chinese patients with ankylosing spondylitis. J Rheumatol. 2003;30:321–5.

    PubMed  CAS  Google Scholar 

  12. Hou TY, Chen HC, Chen CH, Chang DM, Liu FC, Lai JH. Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience. Intern Med J. 2007;37:749–52.

    PubMed  Google Scholar 

  13. Sun GH, Li YL, Xiao XG. Clinical implication of HLA-B*27 subtypes by polymerase chain reaction with sequence specific primers. J Dalian Med Univ. 2006;28:410–3.

    CAS  Google Scholar 

  14. Ma HJ, Hu F. Diversity of human leukocyte antigen-B*27 alleles in Han population of Hunan Province, southern China. Tissue Antigens. 2006;68:163–6.

    Article  PubMed  CAS  Google Scholar 

  15. Xu N, Sun H, San XY, et al. A study on the association of HLA-B*27 subtype with ankylosing spondylitis in Chinese northern Han population. Bei Jing Yi Xue. 2007;29:241–3.

    Google Scholar 

  16. Chen ZJ, Li S. Analysis of HLA-B*27 subtypes in Guangxi Zhuang nationality patients with ankylosing spondylitis. J Guangxi Med Univ. 2007;24:738–9.

    CAS  Google Scholar 

  17. Chen CR, Zhang ZY, Ni HY, et al. A study of HLA-B*27 subtypes and their association with ankylosing spondylitis. Chin J Blood Transfus. 2007;20:13–4.

    Google Scholar 

  18. Yu XY, Gu GH, Gao C, et al. Association analysis on heterogeneity of HLA-B*27 and ankylosing spondylitis. Suzhou Univ J Med Sci. 2006;26:605–8.

    CAS  Google Scholar 

  19. Zhou F, Yu C, Zhang K. Distribution of HLA-B*27 subtypes in Nantong and their association with ankylosing spondylitis. J Mod Lab Med. 2009;24:135–6.

    Google Scholar 

  20. Yu HC, Li ZN, Liu S, Li HH, Qian DM, Wang B. The study on the correlation between HLAB*27 subtype and ankylosing spondylitis. World J Infect. 2007;7:51–2.

    Google Scholar 

  21. Liu Y, Jiang L, Cai Q, et al. Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients. Tissue Antigens. 2009;75:61–4.

    Article  PubMed  Google Scholar 

  22. Mou Y, Wu Z, Gu J, et al. HLA-B27 polymorphism in patients with juvenile and adult-onset ankylosing spondylitis in southern China. Tissue Antigens. 2010;75:56–60.

    Article  PubMed  CAS  Google Scholar 

  23. Liu X, Hu LH, Li YR, Chen FH, Ning Y, Yao QF. The association of HLA-B*27 subtypes with ankylosing spondylitis in Wuhan population of China. Rheumatol Int. 2010;30:587–90.

    Article  PubMed  CAS  Google Scholar 

  24. Park S-H, Kim JH, Kim S-G, Kim S-K, Chung WT, Choe J-Y. Human leucocyte antigen-B27 subtypes in Korean patients with ankylosing spondylitis: higher B*2705 in the patient group. Int J Rheum Dis. 2009;12:34–8.

    Article  PubMed  Google Scholar 

  25. Gonzalez-Roces S, Alvarez MV, Gonzalez S, Dieye A, Makni H, Woodfield DG, Housan L, Konenkov V, Abbadi MC, Grunnet N, Coto E, López-Larrea C. HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis. Tissue Antigens. 1997;49:116–23.

    Article  PubMed  CAS  Google Scholar 

  26. Ren EC, Koh WH, Sim D, Boey ML, Wee GB, Chan SH. Possible protective role of HLA-B*2706 for ankylosing spondylitis. Tissue Antigens. 1997;49:67–9.

    Article  PubMed  CAS  Google Scholar 

  27. Alaez C, Gazit E, Ibarrol B, Yaron M, Livneh A, Avishai O, Gorodezky C. Distribution of HLA-B27 subtypes in ankylosing spondylitis in an Israeli population. Arch Med Res. 2007;38:452–5.

    Article  PubMed  CAS  Google Scholar 

  28. Chavan H, Samant R, Deshpande A, Mankeshwar R. Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis. Int J Rheum Dis. 2011;14:369–74.

    Article  PubMed  Google Scholar 

  29. Acar M, Cora T, Tunc R, Acar H. HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls. Rheumatol Int. 2011. doi:10.1007/s00296-011-2099-0.

  30. Birinci A, Bilgici A, Kuru O, Durupinar B. HLA-B27 polymorphism in Turkish patients with ankylosing spondylitis. Rheumatol Int. 2006;26:285–7.

    Article  PubMed  CAS  Google Scholar 

  31. Diyarbakir E, Eyerci N, Melikoglu M, Topcu A, Pirim I. HLA B27 subtype distribution among patients with ankylosing spondylitis in eastern Turkey. Genet Test Mol Biomarkers. 2012;16:456–8.

    Article  PubMed  CAS  Google Scholar 

  32. Harfouch EI, Al-Cheikh SA. HLA-B27 and its subtypes in Syrian patients with ankylosing spondylitis. Saudi Med J. 2011;32:364–8.

    PubMed  Google Scholar 

  33. Gonzalez S, Garcia-Fernandez S, Martinez-Borra J, Blanco-Gelaz MA, Rodrigo L, Sanchez del Río J, López-Vazquez A, Torre-Alonso JC, López-Larrea C. High variability of HLA-B27 alleles in ankylosing spondylitis and related spondyloarthropathies in the population of northern Spain. Human Immunol. 2002;63:673–6.

    Google Scholar 

  34. López-Larrea C, Blanco-Gelaz MA, Torre-Alonso JC, Bruges Armas J, Suarez-Alvarez B, Pruneda L, Couto AR, Gonzalez S, Lopez-Vázquez A, Martinez-Borra J. Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations. Arthritis Res Ther. 2006;8:1–5.

    Article  Google Scholar 

  35. Varnavidou-Nicolaidou A, Karpasitou K, Georgiou D, Stylianou G, Kokkofitou A, Michalis C, Constantina C, Gregoriadou C, Kyriakides G. HLA-B27 in the Greek Cypriot population: distribution of subtypes in patients with ankylosing spondylitis and other HLA-B27-related diseases. The possible protective role of B*2707. Hum Immunol. 2004;65:1451–4.

    Article  PubMed  CAS  Google Scholar 

  36. López-Larrea C, Gonzalez-Races S, Pefia M, Dominguez O, Coto E, Alvarez V, Moreno M, Hernandez O, Burgos-Vargas R, Gorodezky C. Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset. Hum Immunol. 1995;43:174–80.

    Google Scholar 

  37. Cipriani A, Rivera S, Hassanhi M, Márquez G, Hernández R, Villalobos C, Montiel M. HLA-B27 subtypes determination in patients with ankylosing spondylitis from Zulia, Venezuela. Hum Immunol. 2003;64:745–9.

    Article  PubMed  CAS  Google Scholar 

  38. Kchir MM, Hamdi W, Laadhar L, Kochbati S, KaVel D, Saadellaoui K, Lahmar H, Ghannouchi MM, Azzouz D, Daoud L, Hamida AB, Zouari B, Zitouni M, Makni S. HLA-B, DR and DQ antigens polymorphism in Tunisian patients with ankylosing spondylitis (a case–control study). Rheumatol Int. 2010;30:933–9.

    Article  PubMed  CAS  Google Scholar 

  39. Siala M, Mahfoudh N, Gdoura R, Younes M, Fourati H, Kammoun A, Chour I, Meddeb N, Gaddour L, Hakim F, Baklouti S, Bargaoui N, Sellami S, Hammami A, Makni H. Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia. Rheumatol Int. 2009;29:1193–6.

    Article  PubMed  CAS  Google Scholar 

  40. Dáz-Pena R, Ouédraogo A, López-Vázquez A, Sawadogo SA, López Larrea SA. Ankylosing spondylitis in three sub-Saharan populations: HLA-B*27 and HLA-B*14 contribution. Tissue Antigens. 2012;80:14–5.

    Article  Google Scholar 

  41. Hulsmeyer M, Welfle K, Pohlmann T, Misselwitz R, Alexiev U, Welfle H, Saenger W, Uchanska-Ziegle B, Ziegler A. Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed with a self-peptide. J Mol Biol. 2005;346:1367–79.

    Article  PubMed  Google Scholar 

  42. Van Gaalen FA. Does HLA-B*2706 protect against ankylosing spondylitis? A meta-analysis. Int J Rheum Dis. 2012;15:8–12.

    Article  PubMed  Google Scholar 

  43. Wang-Dong X, Liu S-S, Pan H-F, Ye D-Q. Lack of association of TLR4 polymorphisms with susceptibility to rheumatoid arthritis and ankylosing spondylitis: a meta-analysis. Joint Bone Spine. 2012;. doi:10.1016/j.jbspin.2012.02.012.

    Google Scholar 

  44. Kim TJ, Na KS, Lee HJ, Lee B, Kim TH. HLA-B27 homozygosity has no influence on clinical manifestations and functional disability in ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:574–9.

    PubMed  Google Scholar 

  45. Domínguez-López ML, Ortega-Ortega Y, Manríquez-Raya JC, Burgos-Vargas R, Vega-López A, García-Latorre E. Antibodies against recombinant heat shock proteins of 60 kDa from enterobacteria in the sera and synovial fluid of HLA-B27 positive ankylosing spondylitis patients. Clin Exp Rheumatol. 2009;27:626–32.

    PubMed  Google Scholar 

  46. Zhang L, Liu JL, Zhang YJ, Wang H. Association between HLA-B*27 polymorphisms and ankylosing spondylitis in Han populations: a meta-analysis. Clin Exp Rheumatol. 2011;29:285–92.

    PubMed  CAS  Google Scholar 

  47. Wang J, Pan HF, Hu YT, Zhu Y, He Q. Polymorphism of IL-8 in 251 allele and gastric cancer susceptibility: a meta-analysis. Dig Dis Sci. 2010;55:1818–23.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank all patients with AS and controls who provided the DNA and information necessary for this study. This work was partly supported by grants from the National Natural Science Foundation of China (30771849, 30972530, 81273169).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    Ting Yang, Zhenhua Duan, Shanshan Wu, Si Liu, Zhen Zeng, Guixing Li, Sheng Wang, Dazhi Fan, Dongqing Ye & Faming Pan

  2. Department of Rheumatism and Immunity, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China

    Shengqian Xu

  3. Anhui Medical Genetics Center in Anhui Medical College, Hefei, 230061, Anhui, China

    Li Zhang

Authors
  1. Ting Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhenhua Duan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shanshan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Si Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhen Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guixing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Dazhi Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dongqing Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shengqian Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Li Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Faming Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Faming Pan.

Additional information

T. Yang and Z. Duan contributed equally to this work and should be considered co-first authors.

About this article

Cite this article

Yang, T., Duan, Z., Wu, S. et al. Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: a meta-analysis. Mod Rheumatol (2013). https://doi.org/10.1007/s10165-013-0836-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10165-013-0836-9

Keywords

Search

Navigation