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Association of interleukin-1 receptor-associated kinase (IRAK1) gene polymorphisms (rs3027898, rs1059702) with systemic lupus erythematosus in a Chinese Han population

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Abstract

Objective

The purpose of this study was to examine the association of interleukin-1 receptor-associated kinase (IRAK1) polymorphisms (rs3027898, rs1059702) with systemic lupus erythematosus (SLE) in a Chinese Han population.

Methods

A total of 667 SLE patients and 667 healthy controls were collected in this study. The genotyping of polymorphisms (rs3027898, rs1059702) was determined by TaqMan allele discrimination assay on the 7300 real-time polymerase chain reaction system. The statistical analysis was conducted by chi square test or Fisher’s exact test.

Results

The frequency of C allele for rs3027898 in patients was significantly higher than in controls (C versus A: OR = 1.438, 95 % CI = 1.180–1.753, p < 0.001), and a similar association was shown in rs1059702 (A versus G: OR = 1.383, 95 % CI = 1.143–1.674, p = 0.001). Interestingly, the C allele of rs3027898 was associated with a decreased risk for patients with oral ulcers. However, no significant difference was detected in IRAK1 rs1059702 polymorphism and the clinical manifestations.

Conclusions

Our data demonstrate that the polymorphisms rs3027898 and rs1059702 of IRAK1 gene are associated with SLE in the Chinese Han population.

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References

  1. Jakes RW, Bae SC, Louthrenoo W, Mok CC, Navarra SV, Kwon N. Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features and mortality. Arthritis Care Res (Hoboken). 2012;64:159–68.

    Article  Google Scholar 

  2. Gupta R, Sharma A, Gupta R, Agarwal SK, Dinda AK. Morphometry of non-inflammatory arteriolar changes in lupus nephritis: a study of 40 cases. Saudi J Kidney Dis Transpl. 2012;23:1196–201.

    PubMed  Google Scholar 

  3. Das NK, Dutta RN, Sengupta SR. Skin lesions in lupus erythematosus: a marker of systemic involvement. Indian J Dermatol. 2011;56:537–40.

    Article  PubMed  Google Scholar 

  4. Benseler SM, Silverman ED. Neuropsychiatric involvement in pediatric systemic lupus erythematosus. Lupus. 2007;16:564–71.

    Article  PubMed  CAS  Google Scholar 

  5. Levy DM, Kamphuis S. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am. 2012;59:345–64.

    Article  PubMed  Google Scholar 

  6. Lee HS, Bae SC. What can we learn from genetic studies of systemic lupus erythematosus? Implications of genetic heterogeneity among populations in SLE. Lupus. 2010;19:1452–9.

    Article  PubMed  CAS  Google Scholar 

  7. Weckerle CE, Niewold TB. The unexplained female predominance of systemic lupus erythematosus: clues from genetic and cytokine studies. Clin Rev Allergy Immunol. 2011;40:42–9.

    Article  PubMed  CAS  Google Scholar 

  8. Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta. 2002;1592:265–80.

    Article  PubMed  CAS  Google Scholar 

  9. Jacob CO, Reiff A, Armstrong DL, Myones BL, Silverman E, Klein-Gitelman M, et al. Identification of novel susceptibility genes in childhood-onset systemic lupus erythematosus using a uniquely designed candidate gene pathway platform. Arthritis Rheum. 2007;56:4164–73.

    Article  PubMed  CAS  Google Scholar 

  10. Ringwood L, Li L. The involvement of the interleukin-1 receptor-associated kinases (IRAKs) in cellular signaling networks controlling inflammation. Cytokine. 2008;42:1–7.

    Article  PubMed  CAS  Google Scholar 

  11. Zhu J, Mohan C. Toll-like receptor signaling pathways—therapeutic opportunities. Mediators Inflamm. 2010;. doi:10.1155/2010/781235.

    Google Scholar 

  12. Gottipati S, Rao NL, Fung-Leung WP. IRAK1: a critical signaling mediator of innate immunity. Cell Signal. 2008;20:269–76.

    Article  PubMed  CAS  Google Scholar 

  13. Kollewe C, Mackensen AC, Neumann D, Knop J, Cao P, Li S, et al. Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem. 2004;279:5227–36.

    Article  PubMed  CAS  Google Scholar 

  14. Jacob CO, Zhu J, Armstrong DL, Yan M, Han J, Zhou XJ, et al. Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus. Proc Natl Acad Sci USA. 2009;106:6256–61.

    Article  PubMed  CAS  Google Scholar 

  15. Janssens S, Beyaert R. Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell. 2003;11:293–302.

    Article  PubMed  CAS  Google Scholar 

  16. Dunne A, O’Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE. 2003;. doi:10.1126/stke.2003.171.re3.

    PubMed  Google Scholar 

  17. Thomas JA, Allen JL, Tsen M, Dubnicoff T, Danao J, Liao XC, et al. Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. J Immunol. 1999;163:978–84.

    PubMed  CAS  Google Scholar 

  18. Dieudé P, Bouaziz M, Guedj M, Riemekasten G, Airò P, Müller M, et al. Evidence of the contribution of the X chromosome to systemic sclerosis susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype. Arthritis Rheum. 2011;63:3979–87.

    Article  PubMed  Google Scholar 

  19. Zhang H, Pu J, Wang X, Shen L, Zhao G, Zhuang C, et al. IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis. Rheumatol Int. 2012;. doi:10.1007/s00296-012-2379-3.

    Google Scholar 

  20. Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. A polymorphism in the 3′-UTR of interleukin-1 receptor-associated kinase (IRAK1), a target gene of miR-146a, is associated with rheumatoid arthritis susceptibility. Jt Bone Spine. 2010;77:411–3.

    Article  CAS  Google Scholar 

  21. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40:1725.

    Article  PubMed  CAS  Google Scholar 

  22. Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, et al. Interleukin-1 receptor- associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and T LR9-mediated interferon-α induction. J Exp Med. 2005;201:915–23.

    Article  PubMed  CAS  Google Scholar 

  23. Wang D, Fasciano S, Li L. The interleukin-1 receptor associated kinase 1 contributes to the regulation of NFAT. Mol Immunol. 2008;45:3902–8.

    Article  PubMed  CAS  Google Scholar 

  24. Maitra U, Davis S, Reilly CM, Li L. Differential regulation of Foxp3 and IL-17 expression in CD4 T helper cells by IRAK-1. J Immunol. 2009;182:5763–9.

    Article  PubMed  CAS  Google Scholar 

  25. Thomas JA, Haudek SB, Koroglu T, Tsen MF, Bryant DD, White DJ, et al. IRAK1 deletion disrupts cardiac Toll/IL-1 signaling and protects against contractile dysfunction. Am J Physiol Heart Circ Physiol. 2003;285:H597–606.

    PubMed  CAS  Google Scholar 

  26. Lis J, Jarząb A, Witkowska D. Molecular mimicry in the etiology of autoimmune diseases. Postepy Hig Med Dosw. 2012;66:475–91.

    Article  Google Scholar 

  27. Torres-Carrillo NM, Ruiz-Noa Y, Martínez-Bonilla GE, Leyva-Torres SD, Torres-Carrillo N, Palafox-Sánchez CA, et al. The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett. 2012;147:41–6.

    Article  PubMed  CAS  Google Scholar 

  28. Dieudé P, Guedj M, Wipff J, Avouac J, Hachulla E, Diot E. The PTPN22 620 W allele confers susceptibility to systemic sclerosis: findings of a large case–control study of European Caucasians and a meta-analysis. Arthritis Rheum. 2008;58:2183–8.

    Article  PubMed  Google Scholar 

  29. Lea WW, Lee YH. The association between the PTPN22 C1858T polymorphism and systemic lupus erythematosus: a meta-analysis update. Lupus. 2011;20:51–7.

    Article  PubMed  CAS  Google Scholar 

  30. Chatzikyriakidou A, Voulgari PV, Georgiou I, Drosos AA. The role of microRNA-146a (miR-146a) and its target IL-1R-associated kinase (IRAK1) in psoriatic arthritis susceptibility. Scand J Immunol. 2010;71:382–5.

    Article  PubMed  CAS  Google Scholar 

  31. Liu G, Tsuruta Y, Gao Z, Park YJ, Abraham E. Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity. J Immunol. 2007;179:4125–34.

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81172764); and the Specialized Research Fund for the Doctoral Program of Higher Education of China (20113420110005).

Conflict of interest

The authors report no conflicts of interest.

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Authors and Affiliations

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

    Yu Zhai, Ke Xu, Rui-Xue Leng, Han Cen, Wei Wang, Yan Zhu, Mo Zhou, Chen-Chen Feng & Dong-Qing Ye

  2. Anhui Provincial Laboratory of Population Health and Major Disease Screening and Diagnosis, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Yu Zhai, Ke Xu, Rui-Xue Leng, Han Cen, Wei Wang, Yan Zhu, Mo Zhou, Chen-Chen Feng & Dong-Qing Ye

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  1. Yu Zhai
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Corresponding author

Correspondence to Dong-Qing Ye.

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Responsible Editor: Andras Falus.

Y. Zhai and K. Xu are contributed equally to this work and should be considered co-first authors.

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Zhai, Y., Xu, K., Leng, RX. et al. Association of interleukin-1 receptor-associated kinase (IRAK1) gene polymorphisms (rs3027898, rs1059702) with systemic lupus erythematosus in a Chinese Han population. Inflamm. Res. 62, 555–560 (2013). https://doi.org/10.1007/s00011-013-0607-2

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  • DOI: https://doi.org/10.1007/s00011-013-0607-2

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