Skip to main content

Advertisement

Log in

IL1RN*2 allele of IL-1receptor antagonist VNTR polymorphism is associated with susceptibility to anklyosing spondylitis in Indian patients

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Despite strong linkage of ankylosing spondylitis (AS) with human leukocyte antigen (HLA) B27, its contribution to disease susceptibility is only 15%, and additional genetic factors are likely to be involved in AS. Interleukin (IL)-1 locus has been linked to AS in European population. Thus, we studied IL-1 receptor antagonist polymorphism in Indian patients with AS. One hundred and sixty-two patients with AS and ethnically matched healthy controls were included. IL-1Ra variable number tandem repeat polymorphism was studied by polymerase chain reaction (PCR). HLA B27 was done by amplification refractory mutation system PCR. Clinical details regarding severity of articular disease, presence of peripheral arthritis, and extra-articular manifestations were collected. The mean age of these 162 patients was 35 years, and the mean duration of disease was 10.8 years. Of these162 patients, 137 were HLA B27 positive. The commoner alleles—IL-1RN*1 and IL-1RN*2—together accounted for 99.5% of the IL-1RN alleles in the control population and 98.5% of the cases. The allele frequency as well as the carriage rate of allele IL-1RN*2 were significantly higher in patients with AS than the control populations (26.3 vs 16.2% and 41.97 vs 22.5%, respectively; p = 0.015 and 0.0002). The IL-1RN*2 allele was not associated with any difference in clinical disease expression. The IL-1RN*2 allele is a susceptibility marker for AS in the Indian population but does not influence disease phenotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brown MA, Kennedy LG, MacGregor AJ, MacGregor AJ, Darke C, Duncan E, Shatford JL et al (1997) Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum 40:1823–1828

    Article  PubMed  CAS  Google Scholar 

  2. Laval SH, Timms A, Edwards S, Bradbury L, Brophy S, Milicic A, Rubin L, Siminovitch KA, Weeks DE, Calin A, Wordsworth BP, Brown MA (2001) Whole genome screening in ankylosing spondylitis: evidence of nonMHC genetic susceptibility loci. Am J Hum Gen 68:918–926

    Article  CAS  Google Scholar 

  3. Arend WP, Malyak M, Guthridge CJ, Gabay C (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 16:27–55

    Article  PubMed  CAS  Google Scholar 

  4. Huang CM, Wu MC, Wu JY, Tsai FJ (2002) Interleukin-1 receptor antagonist gene polymorphism in Chinese patients with systemic lupus erythematosus. Clin Rheumatol 21:255–257

    Article  PubMed  Google Scholar 

  5. Cork MJ, Tarlow JK, Blakemore AI, McDonagh JG, Messenger AG, Bleehen SS et al (1993) Genetics of interleukin one receptor antagonists in inflammatory skin diseases. J Invest Dermatol 100:552

    Google Scholar 

  6. Perrier S, Coussediere C, Dubost JJ, Albuisson E, Sauvezie B (1998) IL-1 receptor antagonist (IL-1RA) gene polymorphism in Sjogren’s syndrome and rheumatoid arthritis. Clin Immunol Immunopathol 87:309–313

    Article  PubMed  CAS  Google Scholar 

  7. Meulenbelt I, Seymour AB, Nieuwland M, Huizinga TW, van Duijn CM, Slagboom PE (2004) Association of the interleukin-1 gene cluster with radiographic signs of osteoarthritis of the hip. Arthritis Rheum 50:1179–1186

    Article  PubMed  CAS  Google Scholar 

  8. Vencovsky J, Jarosova K, Ruzickova S, Nemcova D, Niederlova J, Ozen S et al (2001) Higher frequency of allele 2 of the interleukin-1 receptor antagonist gene in patients with juvenile idiopathic arthritis. Arthritis Rheum 44:2387–2391

    Article  PubMed  CAS  Google Scholar 

  9. Grover S, Tandon S, Misra R, Aggarwal A (2006) Interleukin-1 receptor antagonist gene polymorphism in patients with rheumatoid arthritis in India. Indian J Med Res 123:815–820

    PubMed  CAS  Google Scholar 

  10. Arman A, Yilmaz B, Coker A, Inanc N, Direskeneli H (2006) Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkish patients with rheumatoid arthritis. Clin Exp Rheumatol 24:643–648

    PubMed  CAS  Google Scholar 

  11. McGarry F, Neilly J, Anderson R, Sturrock R, Field M (2001) A polymorphism within the interleukin-1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis. Rheumatology 40:1359–1364

    Article  PubMed  CAS  Google Scholar 

  12. van der Paardt M, Crusius JB, García González MA, Baudoin P, Kostense PJ, Alizadeh BZ et al (2002) Interleukin-1b and interleukin-1 receptor antagonist gene polymorphisms in ankylosing spondylitis. Rheumatology 41:1419–1423

    Article  PubMed  Google Scholar 

  13. van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 27:361–368

    Article  PubMed  Google Scholar 

  14. Tonks S, Marsh SG, Bunce M, Bodmer JG (1999) Molecular typing for HLA class I using ARMS-PCR: further developments following the 12th international histocompatibility workshop. Tissue Antigens 53:175–183

    Article  PubMed  CAS  Google Scholar 

  15. Carter MJ, di Giovine FS, Jones S, Mee J, Camp NJ, Lobo AJ et al (2001) Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians. Gut 48:461–467

    Article  PubMed  CAS  Google Scholar 

  16. Schrijver HM, van As J, Crusius JB, Dijkstra CD, Uitdehaag BM (2003) Interleukin (IL)-1 gene polymorphisms: relevance of disease severity associated alleles with IL-1beta and IL-1ra production in multiple sclerosis. Mediat Inflamm 12:89–94

    Article  Google Scholar 

  17. Vamvakopoulos J, Green C, Metcalfe S (2002) Genetic control of IL-1beta bioactivity through differential regulation of the IL-1 receptor antagonist. Eur J Immunol 32:2988–2996

    Article  PubMed  CAS  Google Scholar 

  18. Perrier S, Coussediere C, Dubost JJ, Albuisson E, Sauvezie B (1998) IL-1receptor antagonist (IL-1RA) gene polymorphism in Sjogren’s syndrome and rheumatoidarthritis. Clin Immunol Immunopathol 87:309–313

    Article  PubMed  CAS  Google Scholar 

  19. Redlitz KH, Yamshchikov VF, Cominelli F (2004) Differential contribution of IL-1Ra isoforms to allele-specific IL-1Ra mRNA accumulation. J Interferon Cytokine Res 24:253–260

    Article  PubMed  CAS  Google Scholar 

  20. Santtila S, Savinainen K, Hurme M (1998) Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta production in vitro. Scand J Immunol 47:195–198

    Article  PubMed  CAS  Google Scholar 

  21. Danis VA, Millington M, Hyland V, Grennan D (1995) Cytokine production by normal human monocytes—inter-subject variation and relationship to an IL-1 receptor antagonist (IL-1Ra) gene polymorphism. Clin Exp Immunol 99:303–310

    Article  PubMed  CAS  Google Scholar 

  22. Carter KW, Pluzhnikov A, Timms AE, Miceli-Richard C, Bourgain C, Wordsworth BP, Jean-Pierre H, Cox NJ, Palmer LJ, Breban M, Reveille JD, Brown MA (2007) Combined analysis of three whole genome linkage scans for ankylosing spondylitis. Rheumatology (Oxford) 46:763–771

    Article  CAS  Google Scholar 

  23. Timms AE, Crane AM, Sims AM, Cordell HJ, Bradbury LA, Abbott A, Coyne MR, Beynon O, Herzberg I, Duff GW, Calin A, Cardon LR, Wordsworth BP, Brown MA (2004) The interleukin 1 gene cluster contains a major susceptibility locus for ankylosing spondylitis. Am J Hum Genet 75:587–595

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amita Aggarwal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Agrawal, S., Srivastava, R., Sharma, B. et al. IL1RN*2 allele of IL-1receptor antagonist VNTR polymorphism is associated with susceptibility to anklyosing spondylitis in Indian patients. Clin Rheumatol 27, 573–576 (2008). https://doi.org/10.1007/s10067-007-0748-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-007-0748-1

Keywords

Navigation