Abstract
The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case–control association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4 % and 86.8 %, respectively [T versus C, odds ratio (OR) = 1.287, 95 % confidence interval (CI) = 1.010–1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value = 0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC + CT, OR = 1.368, 95 % CI = 1.050–1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR = 0.734, 95 % CI = 0.573–0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.
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References
Smolen, J.S., G. Steiner, and M. Aringer. 2005. Anti-cytokine therapy in systemic lupus erythematosus. Lupus 14(3): 189–191.
Leonard, W.J., R. Zeng, and R. Spolski. 2008. Interleukin 21: a cytokine/cytokine receptor system that has come of age. Journal of Leukocyte Biology 84(2): 348–356.
Spolski, R., and W.J. Leonard. 2008. The Yin and Yang of interleukin-21 in allergy, autoimmunity and cancer. Current Opinion immunology 20(3): 295–301.
Korn, T., E. Bettelli, W. Gao, A. Awasthi, A. Jäger, T.B. Strom, M. Oukka, and V.K. Kuchroo. 2007. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152): 484–487.
Vogelzang, A., H.M. McGuire, D. Yu, J. Sprent, C.R. Mackay, and C. King. 2008. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 29(1): 127–137.
Ozaki, K., R. Spolski, R. Ettinger, H.P. Kim, G. Wang, C.F. Qi, P. Hwu, D.J. Shaffer, S. Akilesh, D.C. Roopenian, H.C. Morse 3rd, P.E. Lipsky, and W.J. Leonard. 2004. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. Journal of Immunology 173(9): 5361–5371.
Kuchen, S., R. Robbins, G.P. Sims, C. Sheng, T.M. Phillips, P.E. Lipsky, and R. Ettinger. 2007. Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4+ T cell-B cell collaboration. Journal of Immunology 179(9): 5886–5896.
Zwirner, N.W., and C.I. Domaica. 2010. Cytokine regulation of natural killer cell effector functions. Biofactors 36(4): 274–288.
Wong, C.K., P.T. Wong, L.S. Tam, E.K. Li, D.P. Chen, and C.W. Lam. 2010. Elevated production of B cell chemokine CXCL13 is correlated with systemic lupus erythematosus disease activity. Journal of Clinical Immunology 30(1): 45–52.
Bubier, J.A., T.J. Sproule, O. Foreman, R. Spolski, D.J. Shaffer, H.C. Morse 3rd, W.J. Leonard, and D.C. Roopenian. 2009. A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proceedings of the National Academy of Sciences of the United States of America 106(5): 1518–1523.
Herber, D., T.P. Brown, S. Liang, D.A. Young, M. Collins, and K. Dunussi-Joannopoulos. 2007. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. Journal of Immunology 178(6): 3822–3830.
Sawalha, A.H., K.M. Kaufman, J.A. Kelly, A.J. Adler, T. Aberle, J. Kilpatrick, E.K. Wakeland, Q.Z. Li, A.E. Wandstrat, D.R. Karp, J.A. James, J.T. Merrill, P. Lipsky, and J.B. Harley. 2008. Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. Annals of the Rheumatic Diseases 67(4): 458–461.
Maiti, A.K., X. Kim-Howard, P. Viswanathan, L. Guillén, A. Rojas-Villarraga, H. Deshmukh, H. Direskeneli, G. Saruhan-Direskeneli, C. Cañas, G.J. Tobön, A.H. Sawalha, A.C. Cherñavsky, J.M. Anaya, and S.K. Nath. 2010. Confirmation of an association between rs6822844 at the Il2-Il21 region and multiple autoimmune diseases: evidence of a general susceptibility locus. Arthritis and Rheumatism 62(2): 323–329.
Hochberg, M.C. 1997. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis and Rheumatism 40(9): 1725.
Sauna, Z.E., and C. Kimchi-Sarfaty. 2011. Understanding the contribution of synonymous mutations to human disease. Nature Reviews Genetics 12(10): 683–691.
Hughes, T., X. Kim-Howard, J.A. Kelly, K.M. Kaufman, C.D. Langefeld, J. Ziegler, E. Sanchez, R.P. Kimberly, J.C. Edberg, R. Ramsey-Goldman, M. Petri, J.D. Reveille, J. Martín, E.E. Brown, L.M. Vilá, G.S. Alarcón, J.A. James, G.S. Gilkeson, K.L. Moser, P.M. Gaffney, J.T. Merrill, T.J. Vyse, M.E. Alarcón-Riquelme, BIOLUPUS Network, S.K. Nath, J.B. Harley, and A.H. Sawalha. 2011. Fine mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21. Arthritis and Rheumatism 63(6): 1689–1697.
Szeto, C.C., H.Y. Mok, K.M. Chow, T.C. Lee, J.Y. Leung, E.K. Li, T.K. Tsui, S. Yu, and L.S. Tam. 2008. Climatic influence on the prevalence of noncutaneous disease flare in systemic lupus erythematosus in Hong Kong. The Journal of Rheumatology 35(6): 1031–1037.
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This work was supported by grants from the key program of National Natural Science Foundation of China (30830089) and the Dr. Start-up Foundation of Anhui Medical University (no. XJ201014).
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Lei Ding and Song Wang contributed equally to this work and should be considered co-first authors.
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Ding, L., Wang, S., Chen, GM. et al. A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population. Inflammation 35, 1781–1785 (2012). https://doi.org/10.1007/s10753-012-9497-7
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DOI: https://doi.org/10.1007/s10753-012-9497-7