Skip to main content
SpringerLink
Log in

Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis

  • Genes and Disease
  • Published:
Rheumatology International Aims and scope Submit manuscript

A Genes and Disease to this article was published on 21 August 2017

Abstract

Many studies have estimated the correlation between HLA-B27 polymorphisms and ankylosing spondylitis (AS). However, the results were controversial. Therefore, we performed this meta-analysis to determine the association of HLA-B*27 polymorphisms with AS and investigate the impacts of HLA-B27 on the clinical symptoms of AS patients. A comprehensive search was performed in PubMed, Web of Science and Embase databases to retrieve the eligible studies, which addressed the association between HLA-B27 polymorphisms and AS susceptibility. The correlation in fixed-effect model was estimated using the relative risk (RR) and 95% confidence intervals (CI). Finally, 41 studies were included in this meta-analysis, among which 35 studies were used to analyze the correlation between HLA-B27 and AS. And 11 studies were applied to estimate the effects of HLA-B27 on the clinical characteristics of AS patients. Besides, our meta-analysis was composed of 8993 AS patients and 19,254 healthy controls. The results suggested that HLA-B27, HLA-B27*02 and HLA-B27*04 were positively in relation to AS (RRHLA-B27 (95% CI) 16.02 (13.85, 18.54), P < 0.001; RRHLA-B*2702 (95% CI) 1.28 (1.08, 1.53), P = 0.005; RRHLA-B27*04 (95% CI) 1.14 (1.01, 1.29), P = 0.041). Moreover, positive association was observed between HLA-B27 and sex (male) [RR (95% CI) 1.10 (1.05, 1.15), P < 0.001], family history [RR (95% CI) 1.10 (1.06, 1.140), P < 0.001], uveitis [RR (95% CI) 1.07 (1.03, 1.11), P < 0001], peripheral joint involvement [RR (95% CI) 1.04 (1.01,1.07), P = 0.013] and hip joints involvement [RR (95% CI) 1.06 (1.02, 1.10), P = 0.003]. In addition, we also found that HLA-B27*04 showed association with peripheral joint involvement [RR (95% CI) 1.13 (1.05–1.23), P = 0.002]. In conclusion, the current meta-analysis indicates that HLA-B27, especially, its subtypes (HLA-B27*02 and HLA-B27*04) may be potential risk factors for AS.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369:1379–1390

    Article  PubMed  Google Scholar 

  2. Dougados M, Baeten D (2011) Spondyloarthritis. Lancet 377:2127–2137

    Article  PubMed  Google Scholar 

  3. Gao X, Wendling D, Botteman MF, Carter JA, Rao S et al (2012) Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents. J Med Econ 15:1054–1063

    Article  PubMed  Google Scholar 

  4. Jang JH, Ward MM, Rucker AN, Reveille JD, Davis JC Jr et al (2011) Ankylosing spondylitis: patterns of radiographic involvement—a re-examination of accepted principles in a cohort of 769 patients. Radiology 258:192–198

    Article  PubMed  PubMed Central  Google Scholar 

  5. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R et al (2011) 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 70:896–904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Jeong H, Eun YH, Kim IY, Kim H, Ahn JK et al (2016) Drug survival of tumor necrosis factor alpha inhibitors in patients with ankylosing spondylitis in Korea. Korean J Intern Med. doi:10.3904/kjim.2016.042

    Google Scholar 

  7. Liu J, Dong Z, Zhu Q, He D, Ma Y et al (2016) TNF-alpha promoter polymorphisms predict the response to etanercept more powerfully than that to infliximab/adalimumab in spondyloarthritis. Sci Rep 6:32202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cavazzana I, Taraborelli M, Fredi M, Tincani A, Franceschini F (2014) Aseptic meningitis occurring during anti-TNF-alpha therapy in rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 32:732–734

    PubMed  Google Scholar 

  9. Zavada J, Uher M, Sisol K, Forejtova S, Jarosova K et al (2016) A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year: a propensity score-matched cohort study. Ann Rheum Dis 75:96–102

    Article  PubMed  Google Scholar 

  10. Nossent JC, Sagen-Johnsen S, Bakland G (2014) Tumor necrosis factor-alpha promoter-308/238 polymorphism association with less severe disease in ankylosing spondylitis is unrelated to serum TNF-alpha and does not predict TNF inhibitor response. J Rheumatol 41:1675–1682

    Article  CAS  PubMed  Google Scholar 

  11. Bowness P (2015) Hla-B27. Annu Rev Immunol 33:29–48

    Article  CAS  PubMed  Google Scholar 

  12. Kim K, Bang SY, Lee S, Lee HS, Shim SC et al (2015) An HLA-C amino acid variant in addition to HLA-B*27 confers risk for ankylosing spondylitis in the Korean population. Arthritis Res Ther 17:342

    Article  PubMed  PubMed Central  Google Scholar 

  13. Al-Qadi R, Salih SF, AlDoski HJ, Nabeel M, Ali JH et al (2015) Association of HLA-B*27 with ankylosing spondylitis in Kurdish patients. Int J Rheum Dis. doi:10.1111/1756-185X.12605

    PubMed  Google Scholar 

  14. Akassou A, Yacoubi H, Jamil A, Dakka N, Amzazi S et al (2015) Prevalence of HLA-B27 in Moroccan healthy subjects and patients with ankylosing spondylitis and mapping construction of several factors influencing AS diagnosis by using multiple correspondence analysis. Rheumatol Int 35:1889–1894

    Article  CAS  PubMed  Google Scholar 

  15. Diyarbakir E, Eyerci N, Melikoglu M, Topcu A, Pirim I (2012) HLA B27 subtype distribution among patients with ankylosing spondylitis in eastern Turkey. Genet Test Mol Biomark 16:456–458

    Article  CAS  Google Scholar 

  16. Qi J, Li Q, Lin Z, Liao Z, Wei Q et al (2013) Higher risk of uveitis and dactylitis and older age of onset among ankylosing spondylitis patients with HLA-B*2705 than patients with HLA-B*2704 in the Chinese population. Tissue Antigens 82:380–386

    Article  CAS  PubMed  Google Scholar 

  17. Yi L, Wang J, Guo X, Espitia MG, Chen E et al (2013) Profiling of hla-B alleles for association studies with ankylosing spondylitis in the chinese population. Open Rheumatol J 7:51–54

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li H, Li Q, Ji C, Gu J (2016) Ankylosing spondylitis patients with HLA-B*2704 have More uveitis than patients with HLA-B*2705 in a North Chinese population. Ocul Immunol Inflamm 1–5: doi:10.1080/09273948.2016.1188967

  19. Diaz-Pena R, Vidal-Castineira JR, Lopez-Vazquez A, Lopez-Larrea C (2016) HLA-B*40:01 is associated with ankylosing spondylitis in HLA-B27-positive populations. J Rheumatol 43:1255–1256

    Article  PubMed  Google Scholar 

  20. Wei JC, Sung-Ching HW, Hsu YW, Wen YF, Wang WC et al (2015) Interaction between HLA-B60 and HLA-B27 as a better predictor of ankylosing spondylitis in a Taiwanese population. PLoS ONE 10:e0137189

    Article  PubMed  PubMed Central  Google Scholar 

  21. Videm V, Cortes A, Thomas R, Brown MA (2014) Current smoking is associated with incident ankylosing spondylitis—the HUNT population-based Norwegian health study. J Rheumatol 41:2041–2048

    Article  PubMed  Google Scholar 

  22. van Gaalen FA, Verduijn W, Roelen DL, Bohringer S, Huizinga TW et al (2013) Epistasis between two HLA antigens defines a subset of individuals at a very high risk for ankylosing spondylitis. Ann Rheum Dis 72:974–978

    Article  PubMed  Google Scholar 

  23. Acar M, Cora T, Tunc R, Acar H (2012) HLA-B27 subtypes in Turkish patients with ankylosing spondylitis and healthy controls. Rheumatol Int 32:3103–3105

    Article  CAS  PubMed  Google Scholar 

  24. al Attia HM, Sherif AM, Hossain MM, Ahmed YH (1998) The demographic and clinical spectrum of Arab versus Asian patients with ankylosing spondylitis in the UAE. Rheumatol Int 17:193–196

    Article  CAS  PubMed  Google Scholar 

  25. Liu Y, Jiang L, Cai Q, Danoy P, Barnardo MC et al (2010) Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients. Tissue Antigens 75:61–64

    Article  CAS  PubMed  Google Scholar 

  26. Mou Y, Wu Z, Gu J, Liao Z, Lin Z et al (2010) HLA-B27 polymorphism in patients with juvenile and adult-onset ankylosing spondylitis in Southern China. Tissue Antigens 75:56–60

    Article  CAS  PubMed  Google Scholar 

  27. Harfouch EI, Al-Cheikh SA (2011) HLA-B27 and its subtypes in Syrian patients with ankylosing spondylitis. Saudi Med J 32:364–368

    PubMed  Google Scholar 

  28. Cipriani A, Rivera S, Hassanhi M, Marquez G, Hernandez R et al (2003) HLA-B27 subtypes determination in patients with ankylosing spondylitis from Zulia, Venezuela. Hum Immunol 64:745–749

    Article  CAS  PubMed  Google Scholar 

  29. Kchir MM, Hamdi W, Laadhar L, Kochbati S, Kaffel D et al (2010) HLA-B, DR and DQ antigens polymorphism in Tunisian patients with ankylosing spondylitis (a case-control study). Rheumatol Int 30:933–939

    Article  CAS  PubMed  Google Scholar 

  30. Chavan H, Samant R, Deshpande A, Mankeshwar R (2011) Correlation of HLA B27 subtypes with clinical features of ankylosing spondylitis. Int J Rheum Dis 14:369–374

    Article  PubMed  Google Scholar 

  31. Pazar B, Safrany E, Gergely P, Szanto S, Szekanecz Z et al (2010) 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 37:379–384

    Article  CAS  PubMed  Google Scholar 

  32. Ben Radhia K, Ayed-Jendoubi S, Sfar I, Ben Romdhane T, Makhlouf M et al (2008) Distribution of HLA-B*27 subtypes in Tunisians and their association with ankylosing spondylitis. Joint Bone Spine 75:172–175

    Article  PubMed  Google Scholar 

  33. Liu X, Hu LH, Li YR, Chen FH, Ning Y et al (2010) The association of HLA-B*27 subtypes with ankylosing spondylitis in Wuhan population of China. Rheumatol Int 30:587–590

    Article  CAS  PubMed  Google Scholar 

  34. Alaez C, Gazit E, Ibarrola B, Yaron M, Livneh A et al (2007) Distribution of HLA-B27 subtypes in ankylosing spondylitis in an Israeli population. Arch Med Res 38:452–455

    Article  CAS  PubMed  Google Scholar 

  35. Birinci A, Bilgici A, Kuru O, Durupinar B (2006) HLA-B27 polymorphism in Turkish patients with ankylosing spondylitis. Rheumatol Int 26:285–287

    Article  CAS  PubMed  Google Scholar 

  36. Gonzalez S, Garcia-Fernandez S, Martinez-Borra J, Blanco-Gelaz MA, Rodrigo L et al (2002) High variability of HLA-B27 alleles in ankylosing spondylitis and related spondyloarthropathies in the population of northern Spain. Hum Immunol 63:673–676

    Article  CAS  PubMed  Google Scholar 

  37. Lopez-Larrea C, Blanco-Gelaz MA, Torre-Alonso JC, Bruges Armas J, Suarez-Alvarez B et al (2006) Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations. Arthritis Res Ther 8:R101

    Article  PubMed  PubMed Central  Google Scholar 

  38. Varnavidou-Nicolaidou A, Karpasitou K, Georgiou D, Stylianou G, Kokkofitou A et al (2004) 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 65:1451–1454

    Article  CAS  PubMed  Google Scholar 

  39. Lopez-Larrea C, Gonzalez-Roces S, Pena M, Dominguez O, Coto E et al (1995) Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset. Hum Immunol 43:174–180

    Article  CAS  PubMed  Google Scholar 

  40. Gonzalez-Roces S, Alvarez MV, Gonzalez S, Dieye A, Makni H et al (1997) HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis. Tissue Antigens 49:116–123

    Article  CAS  PubMed  Google Scholar 

  41. Ren EC, Koh WH, Sim D, Boey ML, Wee GB et al (1997) Possible protective role of HLA-B*2706 for ankylosing spondylitis. Tissue Antigens 49:67–69

    Article  CAS  PubMed  Google Scholar 

  42. Hou TY, Chen HC, Chen CH, Chang DM, Liu FC et al (2007) Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience. Intern Med J 37:749–752

    PubMed  Google Scholar 

  43. Ma HJ, Hu FP (2006) Diversity of human leukocyte antigen-B27 alleles in Han population of Hunan province, southern China. Tissue Antigens 68:163–166

    Article  CAS  PubMed  Google Scholar 

  44. Chou CT, Chen JM, Hsu CM, Chen SJ (2003) HLA-B27 and its subtypes in 4 Taiwanese aborigine tribes: a comparison to Han Chinese patients with ankylosing spondylitis. J Rheumatol 30:321–325

    CAS  PubMed  Google Scholar 

  45. Park SH, Kim J, Kim SG, Kim SK, Chung WT et al (2009) Human leucocyte antigen-B27 subtypes in Korean patients with ankylosing spondylitis: higher B*2705 in the patient group. Int J Rheum Dis 12:34–38

    Article  PubMed  Google Scholar 

  46. Yang M, Xu M, Pan X, Hu Z, Li Q et al (2013) Epidemiological comparison of clinical manifestations according to HLA-B*27 carrier status of Chinese ankylosing spondylitis patients. Tissue Antigens 82:338–343

    Article  CAS  PubMed  Google Scholar 

  47. Wu Z, Lin Z, Wei Q, Gu J (2009) Clinical features of ankylosing spondylitis may correlate with HLA-B27 polymorphism. Rheumatol Int 29:389–392

    Article  PubMed  Google Scholar 

  48. Sun L, Wu R, Xue Q, Wang F, Lu P (2016) Risk factors of uveitis in ankylosing spondylitis: an observational study. Medicine (Baltimore) 95:e4233

    Article  CAS  Google Scholar 

  49. Yang T, Duan Z, Wu S, Liu S, Zeng Z et al (2014) Association of HLA-B27 genetic polymorphisms with ankylosing spondylitis susceptibility worldwide: a meta-analysis. Modern Rheumatol 24:150–161

    Article  CAS  Google Scholar 

  50. Zhang L, Liu JL, Zhang YJ, Wang H (2011) Association between HLA-B*27 polymorphisms and ankylosing spondylitis in Han populations: a meta-analysis. Clin Exp Rheumatol 29:285–292

    CAS  PubMed  Google Scholar 

  51. Kim TJ, Na KS, Lee HJ, Lee B, Kim TH (2009) HLA-B27 homozygosity has no influence on clinical manifestations and functional disability in ankylosing spondylitis. Clin Exp Rheumatol 27:574–579

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Hai Lin

  2. Department of Evidence-based Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Yi-Zhen Gong

Authors
  1. Hai Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi-Zhen Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hai Lin or Yi-Zhen Gong.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

No procedure in this study has involved human participants.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, H., Gong, YZ. Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis. Rheumatol Int 37, 1267–1280 (2017). https://doi.org/10.1007/s00296-017-3741-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-017-3741-2

Keywords

Search

Navigation