Published: 2016-09-28

Interleukin-7 receptor Thr244Ile gene polymorphism and the risk of systemic lupus erythematosus

Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland

Pawel Piotr Jagodzinski

Head of the Department of Biochemistry and Molecular Biology
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland
Institute of Rheumatology, Warsaw, Poland
Interleukin-7 receptor SNP SLE


Aim. Recently, the IL-7 receptor (IL-7R) C>T (rs6897932) single nucleotide polymorphism (SNP), which causes a Thr244Ile substitution in the IL-7R ?-chain, has been suggested as a risk factor for SLE.
Material and Methods. Using high-resolution melting curve analysis we studied the distribution of the IL-7R C>T polymorphism in SLE patients (n = 281) and control subjects (n = 541) in the Polish population.
Results. We did not find significant differences in the distribution of the IL-7R C>T genotype and alleles between SLE patients and controls. However, in the dominant model (T/T and C/T vs C/C genotypes), we observed a protective effect of the IL-7R C>T polymorphism against the presence of neurological manifestations of SLE [OR = 0.3631 (95% CI = 0.1895–0.6954), p = 0.0017, pcorr = 0.0323] and the presence of anti-Scl-70 antibodies (Ab) [OR = 0.3141 (95% CI = 0.1503–0.6561), p = 0.0014, pcorr = 0.0266].
Conclusion. Our studies suggest that the IL-7R C>T (rs6897932) polymorphism might be involved in the neurological manifestations and the presence of anti-Scl-70 Abs in patients with SLE.


Download data is not yet available.


  1. Lewis JE, Fu SM, Gaskin F. Autoimmunity, end organ damage, and the origin of autoantibodies and autoreactive T cells in systemic lupus erythematosus. Discov Med 2013;15:85–92.
  2. Calero I, Sanz I. Targeting B cells for the treatment of SLE: the beginning of the end or the end of the beginning? Discov Med 2010;10:416–424.
  3. Januchowski R, Wudarski M, Chwalińska-Sadowska H, Jagodzinski PP. Prevalence of ZAP-70, LAT, SLP-76, and DNA methyltransferase 1 expression in CD4+ T cells of patients with systemic lupus erythematosus. Clin Rheumatol 2008;27:21–27.
  4. Muniz Caldas CA, Freire de Carvalho J. The role of environmental factors in the pathogenesis of non-organ-specific autoimmune diseases. Best Pract Res Clin Rheumatol 2012;26:5–11.
  5. Jönsen A, Bengtsson AA, Nived O, Truedsson L, Sturfelt G. Gene-environment interactions in the aetiology of systemic lupus erythematosus. Autoimmunity 2007;40:613–617.
  6. Costa-Reis P, Sullivan KE. Genetics and epigenetics of systemic lupus erythematosus. Curr Rheumatol Rep 2013;15:369.
  7. Zhang J, Zhang Y, Yang J, Zhang L, Sun L, Pan HF et al. Three SNPs in chromosome 11q23.3 are independently associated with systemic lupus erythematosus in Asians. 1. Hum Mol Genet 2014;23:524–533.
  8. Cui Y, Sheng Y, Zhang X. Genetic susceptibility to SLE: recent progress from GWAS. J Autoimmun 2013;41:25–33.
  9. Lundström W, Fewkes NM, Mackall CL. IL-7 in human health and disease. Semin Immunol 2012;24:218–224.
  10. Corfe SA, Paige CJ. The many roles of IL-7 in B cell development; mediator of survival, proliferation and differentiation. Seminars in Immunology 2012;24:198–208.
  11. Hong C, Luckey MA, Park JH. Intrathymic IL-7: the where, when, and why of IL-7 signaling during T cell development. Seminars in Immunology 2012;24:151–158.
  12. Jiang Q, Huang J, Li WQ, Cavinato T, Keller JR, Durum SK. Role of the intracellular domain of IL-7 receptor in T cell development. The Journal of Immunology 2007;178:228–234.
  13. Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 2009;9:480–490.
  14. Walsh ST. Structural insights into the common ?-chain family of cytokines and receptors from the interleukin-7 pathway. Immunol Rev 2012;250:303–316.
  15. Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A et al. for the Multiple Sclerosis Genetics Group. Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet 2007;39:1083–1091.
  16. Lundström W, Highfill S, Walsh ST, Beq S, Morse E, Kockum I et al. Soluble IL7R? potentiates IL-7 bioactivity and promotes autoimmunity. Proc Natl Acad Sci U S A 2013;110:E1761–1770.
  17. Santiago JL, Alizadeh BZ, Martínez A, Espino L, de la Calle H, Fernández-Arquero M et al. Study of the association between the CAPSL-IL7R locus and type 1 diabetes. Diabetologia 2008;51:1653–1658.
  18. Wang XS, Wen PF, Zhang M, Hu LF, Ni J, Qiu LJ et al. Interleukin-7 receptor single nucleotide polymorphism rs6897932 (C/T) and the susceptibility to systemic lupus erythematosus. Inflammation 2014;37:615–620.
  19. Hoffjan S, Beygo J, Akkad DA, Parwez Q, Petrasch-Parwez E, Epplen JT. Analysis of variation in the IL7RA and IL2RA genes in atopic dermatitis. J Dermatol Sci 2009;55:138–140.
  20. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–1277.
  21. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725.
  22. Badot V, Luijten RK, van Roon JA, Depresseux G, Aydin S, Van den Eynde BJ et al. Serum soluble interleukin 7 receptor is strongly associated with lupus nephritis in patients with systemic lupus erythematosus. Ann Rheum Dis 2013;72:453–456.
  23. Kim JS, Cho BA, Sim JH, Shah K, Woo CM, Lee EB et al. IL-7R?low memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2012;51:1587–1594.
  24. Wang YH, Diamond B. B cell receptor revision diminishes the autoreactive B cell response after antigen activation in mice. J Clin Invest 2008;118:2896–2907.
  25. O'Doherty C, Alloza I, Rooney M, Vandenbroeck K. IL7RA polymorphisms and chronic inflammatory arthropathies. Tissue Antigens 2009;74:429–431.
  26. Sombekke MH, van der Voort LF, Kragt JJ, Nielsen JM, Guzel H, Visser A et al. Relevance of IL7R genotype and mRNA expression in Dutch patients with multiple sclerosis. Mult Scler 2011;17:922–930.
  27. Heron M, Grutters JC, van Moorsel CH, Ruven HJ, Huizinga TW, van der Helm-van Mil AH et al. Variation in IL7R predisposes to sarcoid inflammation. Genes Immun 2009;10:647–653.
  28. Shamim Z, Spellman S, Haagenson M, Wang T, Lee SJ, Ryder LP et al. Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor. Scand J Immunol 2013;78:214–220.
  29. Hartling HJ, Thorner LW, Erikstrup C, Zinyama R, Kallestrup P, Gomo E et al. Polymorphisms in the interleukin-7 receptor ? gene and mortality in untreated HIV-infected individuals. AIDS 2013;27:1615–1620.
  30. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, Taylor KD et al. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 2011;43:246–252.
  31. Mells GF, Floyd JA, Morley KI, Cordell HJ, Franklin CS, Shin SY et al. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 2011;43:329–332.
  32. Shamim Z, Ryder LP, Heilmann C, Madsen H, Lauersen H, Andersen PK et al. Genetic polymorphisms in the genes encoding human interleukin-7 receptor-alpha: prognostic significance in allogeneic stem cell transplantation. Bone Marrow Transplant 2006;37:485–491.
  33. Giliani S, Bonfim C, de Saint Basile G, Lanzi G, Brousse N, Koliski A et al. Omenn syndrome in an infant with IL7RA gene mutation. J Pediatr 2006;148:272–274.
  34. Shamim Z, Müller K, Svejgaard A, Poulsen LK, Bodtger U, Ryder LP. Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy. Int J Immunogenet 2007;34:149–151.
  35. McKay FC, Swain LI, Schibeci SD, Rubio JP, Kilpatrick TJ, Heard RN et al. Haplotypes of the interleukin 7 receptor alpha gene are correlated with altered expression in whole blood cells in multiple sclerosis. Genes Immun 2008;9:1–6.
  36. Monti P, Brigatti C, Krasmann M, Ziegler AG, Bonifacio E. Concentration and activity of the soluble form of the interleukin-7 receptor ? in type 1 diabetes identifies an interplay between hyperglycemia and immune function. Diabetes 2013;62:2500–2508.
  37. Kreft KL, Verbraak E, Wierenga-Wolf AF, van Meurs M, Oostra BA, Laman JD et al. Decreased systemic IL-7 and soluble IL-7R? in multiple sclerosis patients. Genes Immun 2012;13:587–592.

How to Cite

Jagodzinski PP, Piotrowski P, Olesińska M. Interleukin-7 receptor Thr244Ile gene polymorphism and the risk of systemic lupus erythematosus. JMS [Internet]. 2016Sep.28 [cited 2020Aug.9];85(3):192-6. Available from: