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Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population

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Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 (IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio = 1.20, 95 % confidence interval = 1.02–1.40). However, no significant difference in genotype distribution was found between cases and controls (P = 0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P = 0.06; TT versus TC + CC, P = 0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population.

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References

  1. Münz, C., J.D. Lünemann, M.T. Getts, and S.D. Miller. 2009. Antiviral immune responses: triggers of or triggered by autoimmunity? Nature Reviews Immunology 9: 246–258.

    Article  PubMed  Google Scholar 

  2. Takeuchi, O., and S. Akira. 2010. Pattern recognition receptors and inflammation. Cell 140: 805–820.

    Article  PubMed  CAS  Google Scholar 

  3. Stetson, D.B., and R. Medzhitov. 2006. Antiviral defense: interferons and beyond. The Journal of Experimental Medicine 203: 1837–1841.

    Article  PubMed  CAS  Google Scholar 

  4. Chistiakov, D.A. 2010. Interferon induced with helicase C domain 1 (IFIH1) and virus-induced autoimmunity: a review. Viral Immunology 23: 3–15.

    Article  PubMed  CAS  Google Scholar 

  5. Yoneyama, M., M. Kikuchi, K. Matsumoto, T. Imaizumi, M. Miyagishi, K. Taira, E. Foy, Y.M. Loo, M. Gale Jr., S. Akira, S. Yonehara, A. Kato, and T. Fujita. 2005. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. Journal of Immunology 175: 2851–2858.

    CAS  Google Scholar 

  6. Smyth, D.J., J.D. Cooper, R. Bailey, S. Field, O. Burren, L.J. Smink, C. Guja, C. Ionescu-Tirgoviste, B. Widmer, D.B. Dunger, D.A. Savage, N.M. Walker, D.G. Clayton, and J.A. Todd. 2006. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nature Genetics 38: 617–619.

    Article  PubMed  CAS  Google Scholar 

  7. Gregersen, P.K., and L.M. Olsson. 2009. Recent advances in the genetics of autoimmune disease. Annual Review of Immunology 27: 363–391.

    Article  PubMed  CAS  Google Scholar 

  8. International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), J.B. Harley, M.E. Alarcón-Riquelme, L.A. Criswell, C.O. Jacob, R.P. Kimberly, K.L. Moser, B.P. Tsao, T.J. Vyse, C.D. Langefeld, S.K. Nath, J.M. Guthridge, B.L. Cobb, D.B. Mirel, M.C. Marion, A.H. Williams, J. Divers, W. Wang, S.G. Frank, B. Namjou, S.B. Gabriel, A.T. Lee, P.K. Gregersen, T.W. Behrens, K.E. Taylor, M. Fernando, R. Zidovetzki, P.M. Gaffney, J.C. Edberg, J.D. Rioux, J.O. Ojwang, J.A. James, J.T. Merrill, G.S. Gilkeson, M.F. Seldin, H. Yin, E.C. Baechler, Q.Z. Li, E.K. Wakeland, G.R. Bruner, K.M. Kaufman, and J.A. Kelly. 2008. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nature Genetics 40: 204–210.

    Article  PubMed  CAS  Google Scholar 

  9. Gateva, V., J.K. Sandling, G. Hom, K.E. Taylor, S.A. Chung, X. Sun, W. Ortmann, R. Kosoy, R.C. Ferreira, G. Nordmark, I. Gunnarsson, E. Svenungsson, L. Padyukov, G. Sturfelt, A. Jönsen, A.A. Bengtsson, S. Rantapää-Dahlqvist, E.C. Baechler, E.E. Brown, G.S. Alarcón, J.C. Edberg, R. Ramsey-Goldman, G. McGwin Jr., J.D. Reveille, L.M. Vilá, R.P. Kimberly, S. Manzi, M.A. Petri, A. Lee, P.K. Gregersen, M.F. Seldin, L. Rönnblom, L.A. Criswell, A.C. Syvänen, T.W. Behrens, and R.R. Graham. 2009. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nature Genetics 41: 1228–1233.

    Article  PubMed  CAS  Google Scholar 

  10. Cunninghame Graham, D.S., D.L. Morris, T.R. Bhangale, L.A. Criswell, A.C. Syvänen, L. Rönnblom, T.W. Behrens, R.R. Graham, and T.J. Vyse. 2011. Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with systemic lupus erythematosus. PLoS Genetics 7: e1002341.

    Article  PubMed  CAS  Google Scholar 

  11. Gono, T., Y. Kawaguchi, T. Sugiura, T. Furuya, M. Kawamoto, M. Hanaoka, and H. Yamanaka. 2010. Interferon-induced helicase (IFIH1) polymorphism with systemic lupus erythematosus and dermatomyositis/polymyositis. Modern Rheumatology 20: 466–470.

    Article  PubMed  CAS  Google Scholar 

  12. Hochberg, M.C. 1997. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism 40: 1725.

    Article  PubMed  CAS  Google Scholar 

  13. Kang, D.C., R.V. Gopalkrishnan, Q. Wu, E. Jankowsky, A.M. Pyle, and P.B. Fisher. 2002. mda-5: an interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proceedings of the National Academy of Sciences of the United States of America 99: 637–642.

    Article  PubMed  CAS  Google Scholar 

  14. Meylan, E., J. Tschopp, and M. Karin. 2006. Intracellular pattern recognition receptors in the host response. Nature 442: 39–44.

    Article  PubMed  CAS  Google Scholar 

  15. Kato, H., O. Takeuchi, S. Sato, M. Yoneyama, M. Yamamoto, K. Matsui, S. Uematsu, A. Jung, T. Kawai, K.J. Ishii, O. Yamaguchi, K. Otsu, T. Tsujimura, C.S. Koh, C. Reis e Sousa, Y. Matsuura, T. Fujita, and S. Akira. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441: 101–105.

    Article  PubMed  CAS  Google Scholar 

  16. Baechler, E.C., F.M. Batliwalla, G. Karypis, P.M. Gaffney, W.A. Ortmann, K.J. Espe, K.B. Shark, W.J. Grande, K.M. Hughes, V. Kapur, P.K. Gregersen, and T.W. Behrens. 2003. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proceedings of the National Academy of Sciences of the United States of America 100: 2610–2615.

    Article  PubMed  CAS  Google Scholar 

  17. Bennett, L., A.K. Palucka, E. Arce, V. Cantrell, J. Borvak, J. Banchereau, and V. Pascual. 2003. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. The Journal of Experimental Medicine 197: 711–723.

    Article  PubMed  CAS  Google Scholar 

  18. Santiago-Raber, M.L., R. Baccala, K.M. Haraldsson, D. Choubey, T.A. Stewart, D.H. Kono, and A.N. Theofilopoulos. 2003. Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. The Journal of Experimental Medicine 197: 777–788.

    Article  PubMed  CAS  Google Scholar 

  19. Nacionales, D.C., K.M. Kelly-Scumpia, P.Y. Lee, J.S. Weinstein, R. Lyons, E. Sobel, M. Satoh, and W.H. Reeves. 2007. Deficiency of the type I interferon receptor protects mice from experimental lupus. Arthritis and Rheumatism 56: 3770–3783.

    Article  PubMed  CAS  Google Scholar 

  20. Richez, C., K. Yasuda, R.G. Bonegio, A.A. Watkins, T. Aprahamian, P. Busto, R.J. Richards, C.L. Liu, R. Cheung, P.J. Utz, A. Marshak-Rothstein, and I.R. Rifkin. 2010. IFN regulatory factor 5 is required for disease development in the FcgammaRIIB−/−Yaa and FcgammaRIIB−/− mouse models of systemic lupus erythematosus. Journal of Immunology 184: 796–806.

    Article  CAS  Google Scholar 

  21. Crampton, S.P., J.A. Deane, L. Feigenbaum, and S. Bolland. 2012. Ifih1 gene dose effect reveals MDA5-mediated chronic type I IFN gene signature, viral resistance, and accelerated autoimmunity. Journal of Immunology 188: 1451–1459.

    Article  CAS  Google Scholar 

  22. Liu, S., H. Wang, Y. Jin, R. Podolsky, M.V. Reddy, J. Pedersen, B. Bode, J. Reed, D. Steed, S. Anderson, P. Yang, A. Muir, L. Steed, D. Hopkins, Y. Huang, S. Purohit, C.Y. Wang, A.K. Steck, A. Montemari, G. Eisenbarth, M. Rewers, and J.X. She. 2009. IFIH1 polymorphisms are significantly associated with type 1 diabetes and IFIH1 gene expression in peripheral blood mononuclear cells. Human Molecular Genetics 18: 358–365.

    Article  PubMed  CAS  Google Scholar 

  23. Zouk, H., L. Marchand, and C. Polychronakos. 2010. Study of transcriptional effects in Cis at the IFIH1 locus. PLoS One 5: e11564.

    Article  PubMed  Google Scholar 

  24. Marinou, I., D.S. Montgomery, M.C. Dickson, M.H. Binks, D.J. Moore, D.E. Bax, and A.G. Wilson. 2007. The interferon induced with helicase domain 1 A946T polymorphism is not associated with rheumatoid arthritis. Arthritis Research & Therapy 9: R40.

    Article  Google Scholar 

  25. Robinson, T., S.N. Kariuki, B.S. Franek, M. Kumabe, A.A. Kumar, M. Badaracco, R.A. Mikolaitis, G. Guerrero, T.O. Utset, B.E. Drevlow, L.S. Zaacks, J.S. Grober, L.M. Cohen, K.A. Kirou, M.K. Crow, M. Jolly, and T.B. Niewold. 2011. Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-α and serologic autoimmunity in lupus patients. Journal of Immunology 187: 1298–1303.

    Article  CAS  Google Scholar 

  26. Rönnblom, L., G.V. Alm, and M.L. Eloranta. 2011. The type I interferon system in the development of lupus. Seminars in Immunology 23: 113–121.

    Article  PubMed  Google Scholar 

  27. Han, J.W., H.F. Zheng, Y. Cui, L.D. Sun, D.Q. Ye, Z. Hu, J.H. Xu, Z.M. Cai, W. Huang, G.P. Zhao, H.F. Xie, H. Fang, Q.J. Lu, J.H. Xu, X.P. Li, Y.F. Pan, D.Q. Deng, F.Q. Zeng, Z.Z. Ye, X.Y. Zhang, Q.W. Wang, F. Hao, L. Ma, X.B. Zuo, F.S. Zhou, W.H. Du, Y.L. Cheng, J.Q. Yang, S.K. Shen, J. Li, Y.J. Sheng, X.X. Zuo, W.F. Zhu, F. Gao, P.L. Zhang, Q. Guo, B. Li, M. Gao, F.L. Xiao, C. Quan, C. Zhang, Z. Zhang, K.J. Zhu, Y. Li, D.Y. Hu, W.S. Lu, J.L. Huang, S.X. Liu, H. Li, Y.Q. Ren, Z.X. Wang, C.J. Yang, P.G. Wang, W.M. Zhou, Y.M. Lv, A.P. Zhang, S.Q. Zhang, D. Lin, Y. Li, H.Q. Low, M. Shen, Z.F. Zhai, Y. Wang, F.Y. Zhang, S. Yang, J.J. Liu, and X.J. Zhang. 2009. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nature Genetics 41: 1234–1237.

    Article  PubMed  CAS  Google Scholar 

  28. Yang, W., N. Shen, D.Q. Ye, Q. Liu, Y. Zhang, X.X. Qian, N. Hirankarn, D. Ying, H.F. Pan, C.C. Mok, T.M. Chan, R.W. Wong, K.W. Lee, M.Y. Mok, S.N. Wong, A.M. Leung, X.P. Li, Y. Avihingsanon, C.M. Wong, T.L. Lee, M.H. Ho, P.P. Lee, Y.K. Chang, P.H. Li, R.J. Li, L. Zhang, W.H. Wong, I.O. Ng, C.S. Lau, P.C. Sham, Y.L. Lau, and Asian Lupus Genetics Consortium. 2010. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genetics 6: e1000841.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the key program of National Natural Science Foundation of China (30830089). We wish to thank the patients and healthy control subjects for their cooperation.

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Authors and Affiliations

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

    Han Cen, Rui-Xue Leng, Wei Wang, Mo Zhou, Chen-Chen Feng, Yan Zhu, Xiao-Ke Yang, Mei Yang, Yu Zhai, Bao-Zhu Li, Juan Liu, Hai-Feng Pan & Dong-Qing Ye

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

    Han Cen, Rui-Xue Leng, Wei Wang, Mo Zhou, Chen-Chen Feng, Yan Zhu, Xiao-Ke Yang, Mei Yang, Yu Zhai, Bao-Zhu Li, Juan Liu, Hai-Feng Pan & Dong-Qing Ye

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  1. Han Cen
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Correspondence to Dong-Qing Ye.

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Cen, H., Leng, RX., Wang, W. et al. Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population. Inflammation 36, 444–448 (2013). https://doi.org/10.1007/s10753-012-9564-0

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