Skip to main content
SpringerLink
Log in

Association of rs10954213 polymorphisms and haplotype diversity in interferon regulatory factor 5 with systemic lupus erythematosus: A meta-analysis

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

The rs10954213 polymorphism and the haplotype diversity in interferon regulatory factor 5 (IRF5) play a special role in systemic lupus erythematosus (SLE) but with inconclusive results. We conducted a meta-analysis integrating case-control and haplotype variant studies in multiple ethnic populations to clearly discern the effect of these two variants on SLE. Eleven studies on the relation between rs10954213 polymorpisms in IRF5 and SLE were included and we selected a random effect model to calculate the pooled odds ratios (ORs) and the corresponding 95% confidence interval (95% CI). A total of 6982 cases and 8077 controls were involved in the meta-analysis. The pooled results indicated that A allele was significantly associated with increased risk of SLE as compared with the IRF5 rs10954213 G allele (A vs. G, P<0.00001) in all subjects. The same pattern of the results was also obtained in the European, African American, and Latin American. Asian population had a much lower prevalence of the A allele (49.1%) than any other population studied, and Europeans had the highest frequency of the IRF5 rs10954213 A allele (62.1%). The significant association of increased SLE risk and TCA haplotype was indicated in the contrast of TCA vs. TTA as the pooled OR was 2.14 (P=0.002). The same result was also found in the contrast of TCA vs. TTG as the pooled OR was 1.45 (P=0.004). This meta-analysis suggests that the A allele of rs10954213 and TCA haplotype (rs2004640-rs2070197-rs10954213) in IRF5 is associated with the increased risk of SLE in different ethnic groups, and its prevalence is ethnicity dependent.

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

Similar content being viewed by others

References

  1. Blanco P, Palucka AK, Gill M, et al. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science, 2001,294(5546):1540–1543

    Article  PubMed  CAS  Google Scholar 

  2. Ronnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J Exp Med, 2001,194(12):F59–63

    Article  PubMed  CAS  Google Scholar 

  3. Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci USA, 2003,100(5): 2610–2615

    Article  PubMed  CAS  Google Scholar 

  4. Harley JB, Kelly JA, Kaufman KM. Unraveling the genetics of systemic lupus erythematosus. Springer Semin Immunopathol, 2006,28(2):119–130

    Article  PubMed  CAS  Google Scholar 

  5. Obermoser G, Pascual V. The interferon-alpha signature of systemic lupus erythematosus. Lupus, 2010,19(9): 1012–1019

    Article  PubMed  CAS  Google Scholar 

  6. Crow MK. Interferon pathway activation in systemic lupus erythematosus. Curr Rheumatol Rep, 2005,7(6): 463–468

    Article  PubMed  CAS  Google Scholar 

  7. Petri M, Singh S, Tesfasyone H, et al. Longitudinal expression of type I interferon responsive genes in systemic lupus erythematosus. Lupus, 2009,18(11): 980–989

    Article  PubMed  CAS  Google Scholar 

  8. Banchereau J, Pascual V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity, 2006,25(3):383–392

    Article  PubMed  CAS  Google Scholar 

  9. Kawasaki M, Fujishiro M, Yamaguchi A, et al. Possible role of the JAK/STAT pathways in the regulation of T cell-interferon related genes in systemic lupus erythematosus. Lupus, 2011,20(12):1231–1239

    Article  PubMed  CAS  Google Scholar 

  10. Graham RR, Kozyrev SV, Baechler EC, et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet, 2006,38(5):550–555

    Article  PubMed  CAS  Google Scholar 

  11. Graham RR, Kyogoku C, Sigurdsson S, et al. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci USA, 2007,104(16):6758–6763

    Article  PubMed  CAS  Google Scholar 

  12. Ferreiro-Neira I, Calaza M, Alonso-Perez E, et al. Opposed independent effects and epistasis in the complex association of IRF5 to SLE. Genes Immun, 2007,8(5): 429–438

    Article  PubMed  CAS  Google Scholar 

  13. Kawasaki A, Kyogoku C, Ohashi J, et al. Association of IRF5 polymorphisms with systemic lupus erythematosus in a Japanese population: support for a crucial role of intron 1 polymorphisms. Arthritis Rheum, 2008,58(3): 826–834

    Article  PubMed  CAS  Google Scholar 

  14. Kelly JA, Kelley JM, Kaufman KM, et al. Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans. Genes Immun, 2008,9(3):187–194

    Article  PubMed  CAS  Google Scholar 

  15. Taniguchi T, Ogasawara K, Takaoka A, et al. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol, 2001,19:623–655

    Article  PubMed  CAS  Google Scholar 

  16. Vuong MT, Gunnarsson I, Lundberg S, et al. Genetic risk factors in lupus nephritis and IgA nephropathy-no support of an overlap. PLoS One, 2010,5(5):e10559

    Article  PubMed  Google Scholar 

  17. Song WQ, Li HH, Chen HB, et al. Relationship between polymorphism sites of IRF5, TLR-9 and SLE patients in Shandong Han population. Zhonghua Yi Xue Za Zhi (Chinese), 2009,89(43):3038–3042

    CAS  Google Scholar 

  18. Löfgren SE, Yin H, Delgado-Vega AM, et al. Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells. J Rheumatol, 2010,37(3):574–578

    Article  PubMed  Google Scholar 

  19. Hellquist A, Jarvinen TM, Koskenmies S, et al. Evidence for genetic association and interaction between the TYK2 and IRF5 genes in systemic lupus erythematosus. J Rheumatol, 2009,36(8):1631–1638

    Article  PubMed  CAS  Google Scholar 

  20. Sigurdsson S, Goring HH, Kristjansdottir G, et al. Comprehensive evaluation of the genetic variants of interferon regulatory factor 5 (IRF5) reveals a novel 5 bp length polymorphism as strong risk factor for systemic lupus erythematosus. Hum Mol Genet, 2008,17(6): 872–881

    Article  PubMed  CAS  Google Scholar 

  21. Reddy MV, Velazquez-Cruz R, Baca V, et al. Genetic association of IRF5 with SLE in Mexicans: higher frequency of the risk haplotype and its homozygozity than Europeans. Hum Genet, 2007,121(6):721–727

    Article  PubMed  Google Scholar 

  22. Kozyrev SV, Lewen S, Reddy PM, et al. Structural insertion/deletion variation in IRF5 is associated with a risk haplotype and defines the precise IRF5 isoforms expressed in systemic lupus erythematosus. Arthritis Rheum, 2007,56(4):1234–1241

    Article  PubMed  CAS  Google Scholar 

  23. Siu HO, Yang W, Lau CS, et al. Association of a haplotype of IRF5 gene with systemic lupus erythematosus in Chinese. J Rheumatol, 2008,35(2): 360–362

    PubMed  CAS  Google Scholar 

  24. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002,21(11):1539–1558

    Article  PubMed  Google Scholar 

  25. Zintzaras E, Chatzoulis DZ, Karabatsas CH, et al. The relationship between C677T methylenetetrahydrofolate reductase gene polymorphism and retinopathy in type 2 diabetes: a meta-analysis. J Hum Genet, 2005,50(6): 267–275

    Article  PubMed  CAS  Google Scholar 

  26. Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997,315(7109):629–634

    Article  PubMed  CAS  Google Scholar 

  27. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomised clinical trials: is blinding necessary? Control Clin Trials, 1996,17(1):1–12

    Article  PubMed  CAS  Google Scholar 

  28. Liu K, Liu J, Huang Y, et al. Alpha-adducin Gly460Trp polymorphism and hypertension risk: a meta-analysis of 22 studies including 14303 cases and 15961 controls. PLoS One, 2010,5(9):e13057

    Article  PubMed  Google Scholar 

  29. Hu W, Ren H. A meta-analysis of the association of IRF5 polymorphism with systemiclupus erythematosus. Int J Immunogenet, 2011,38(5): 411–417

    Article  PubMed  CAS  Google Scholar 

  30. Barnes BJ, Richards J, Mancl M, et al. Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. J Biol Chem, 2004,279(43):45 194–45 207

    Article  CAS  Google Scholar 

  31. Honda K, Yanai H, Takaoka A, et al. Regulation of the type I IFN induction: a current view. Int Immunol, 2005,17(11):1367–1378

    Article  PubMed  CAS  Google Scholar 

  32. Takaoka A, Yanai H, Kondo S, et al. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature, 2005,434(7030):243–249

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Hui-feng Liu  (刘辉峰), Xiang-jie An  (安湘杰), Liu Yang  (杨 柳), Yan Li  (李 延), Chang-zheng Huang  (黄长征), Juan Tao  (陶 娟) & Ya-ting Tu  (涂亚庭)

  2. Wuhan Institute of Dermatosis and Venereal Disease Preventing, Wuhan, 430015, China

    Hui-feng Liu  (刘辉峰)

  3. Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yan Yang  (杨 艳)

Authors
  1. Hui-feng Liu  (刘辉峰)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiang-jie An  (安湘杰)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Yang  (杨 艳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liu Yang  (杨 柳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yan Li  (李 延)
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chang-zheng Huang  (黄长征)
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan Tao  (陶 娟)
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ya-ting Tu  (涂亚庭)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ya-ting Tu  (涂亚庭).

Additional information

These authors contributed equally to this work.

This study was supported by the Program for New Century Excellent Talents from the Ministry of Education of China (No. NCET-09-0390).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, Hf., An, Xj., Yang, Y. et al. Association of rs10954213 polymorphisms and haplotype diversity in interferon regulatory factor 5 with systemic lupus erythematosus: A meta-analysis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 15–21 (2013). https://doi.org/10.1007/s11596-013-1064-4

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-013-1064-4

Key words

Search

Navigation