Rheumatology International

, Volume 33, Issue 5, pp 1165–1176 | Cite as

IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis clinical manifestations in the northern Italian population

  • Maria Grazia Catanoso
  • Luigi Boiardi
  • Pierluigi Macchioni
  • Paolo Garagnani
  • Marco Sazzini
  • Sara De Fanti
  • Enrico Farnetti
  • Bruno Casali
  • Ilaria Chiarolanza
  • Davide Nicoli
  • Donata Luiselli
  • Carlo SalvaraniEmail author
Original Article


To investigate the genetic variability of IL-17A, IL17-RA, IL-23A and IL-23R genes on an in-depth phenotypically characterized northern Italian Psoriatic arthritis (PsA) case–control cohort, in search for associations specific to different PsA clinical sub-phenotypes. We examined 118 patients with PsA according to CASPAR criteria (mean age 57 ± 13, female 38.4 %, mean disease duration 13.9 ± 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5 %, radiological erosive disease 49 %) compared with 248 controls of the same ethnic origin matched for age and sex. The presence of axial disease was defined by the clinical axial involvement and/or the presence of radiological alteration consistent with spondyloarthropathy according to New York criteria. The presence of peripheral disease (arthritis and/or enthesitis) was defined only on clinical basis. A total of 40 SNPs, mapping within the genes mentioned above, were genotyped in both groups and used to perform association analyses by subdividing the PsA sample into subgroups according to different clinical manifestations on the basis of axial and peripheral involvements. No differences between patients and controls were found in the distribution of the IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants. Comparing patients with axial disease versus those without, we found that axial manifestations were significantly associated with the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p corr = 0.019, OR 2.63 [95 % CI 1.13–6.16]). No differences in distribution of the allelic variants were found comparing patients with versus those without peripheral disease or patients with versus without radiological peripheral erosions. In PA patients of northern Italian origin, IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants are not associated with disease susceptibility. However, a strong association with the IL-23RA rs12401432 GG genotype is associated with axial involvement of the disease.


Psoriatic arthritis Axial and peripheral involvement Polymorphism il-17 and il-23 cytokines 



This work was supported by Grants RFO ex 60 % University of Bologna to D.L.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

296_2012_2501_MOESM1_ESM.doc (554 kb)
Supplementary material 1 (DOC 553 kb)


  1. 1.
    Wright V, Moll JMH (1976) Psoriatic arthritis. In: Wright V, Moll JMH (eds) Seronegative polyarthritis. North Holland Publishing Co, Amsterdam, pp 169–223Google Scholar
  2. 2.
    Gladman DD (1998) Clinical aspects of the spondyloarthropathies. Am J Med Sci 316:234–238PubMedCrossRefGoogle Scholar
  3. 3.
    Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H (2006) CASPAR Study Group: classification criteria for Psoriatic Arthritis: new criteria from a large international study. Arthritis Rheum 54:2665–2673PubMedCrossRefGoogle Scholar
  4. 4.
    Moll JM, Wright V (1973) Familial occurrence of psoriatic arthritis. Ann Rheum Dis 32:181–201PubMedCrossRefGoogle Scholar
  5. 5.
    Myers A, Kay LJ, Lynch SA, Walker DJ (2005) Recurrence risk for psoriasis and psoriatic arthritis within sibships. Rheumatology (Oxford) 44:773–776CrossRefGoogle Scholar
  6. 6.
    Chandran V, Schentag CT, Brockbank JE et al (2009) Familial aggregation of psoriatic arthritis. Ann Rheum Dis 68:664–667PubMedCrossRefGoogle Scholar
  7. 7.
    Karason A, Love TJ, Gudbjornsson B (2009) A strong heritability of psoriatic arthritis over four generations: the Reykjavik Psoriatic Arthritis Study. Rheumatology (Oxford) 48:1424–1428CrossRefGoogle Scholar
  8. 8.
    Gladman DD, Farewell VT (2003) HLA studies in psoriatic arthritis: current situation and future needs. J Rheumatol 30:4–6PubMedGoogle Scholar
  9. 9.
    Korendowych E, Dixey J, Cox B, Jones S, McHugh N (2003) The influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. J Rheumatol 30:96–101PubMedGoogle Scholar
  10. 10.
    Ho PY, Barton A, Worthington J, Thomson W, Silman AJ, Bruce IN (2007) HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis. Ann Rheum Dis 66:807–811PubMedCrossRefGoogle Scholar
  11. 11.
    Chandran V, Rahman P (2010) Update on the genetics of spondyloarthritis—ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol 24:579–588PubMedCrossRefGoogle Scholar
  12. 12.
    Castelino M, Barton A (2010) Genetic susceptibility factors for psoriatic arthritis. Curr Opin Rheumatol 22:152–156PubMedCrossRefGoogle Scholar
  13. 13.
    Boniface K, Blom B, Liu YJ, de Waal Malefyt R (2008) From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev 226:132–146PubMedCrossRefGoogle Scholar
  14. 14.
    Cargill M, Schrodi SJ, Chang M et al (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80:273–290PubMedCrossRefGoogle Scholar
  15. 15.
    Liu Y, Helms C, Liao W et al (2008) A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet 4:e1000041PubMedCrossRefGoogle Scholar
  16. 16.
    Filer C, Ho P, Smith RL et al (2008) Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis Rheum 58:3705–3709PubMedCrossRefGoogle Scholar
  17. 17.
    Rahman P, Inman RD, Maksymowych WP, Reeve JP, Peddle L, Gladman DD (2009) Association of interleukin 23 receptor variants with psoriatic arthritis. J Rheumatol 36:137–140PubMedGoogle Scholar
  18. 18.
    Hüffmeier U, Lascorz J, Böhm B et al (2009) Genetic variants of the IL-23R pathway: association with psoriatic arthritis and psoriasis vulgaris, but no specific risk factor for arthritis. J Invest Dermatol 129:355–358PubMedCrossRefGoogle Scholar
  19. 19.
    Leipe J, Grunke M, Dechant C et al (2010) Role of Th17 cells in human autoimmune arthritis. Arthritis Rheum 62:2876–2885PubMedCrossRefGoogle Scholar
  20. 20.
    Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888–898PubMedCrossRefGoogle Scholar
  21. 21.
    Balding J, Kane D, Livingstone W et al (2003) Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. Arthritis Rheum 48:1408–1413PubMedCrossRefGoogle Scholar
  22. 22.
    Rahman P, Snelgrove T, Peddle L, Siannis F, Farewell V, Schentag C, Gladman D (2008) A variant of the IL4 I50 V single-nucleotide polymorphism is associated with erosive joint disease in psoriatic arthritis. Arthritis Rheum 58:2207–2208PubMedCrossRefGoogle Scholar
  23. 23.
    Juneblad K, Johansson M, Rantapää-Dahlqvist S, Alenius GM (2011) Association between the PTPN22 +1858 C/T polymorphism and psoriatic arthritis. Arthritis Res Ther 13:R45 (Epub ahead of print)PubMedCrossRefGoogle Scholar
  24. 24.
    Docampo E, Giardina E, Riveira-Muñoz E et al (2011) Deletion of LCE3C and LCE3B is a susceptibility factor for psoriatic arthritis: a study in Spanish and Italian populations and meta-analysis. Arthritis Rheum 63:1860–1865PubMedCrossRefGoogle Scholar
  25. 25.
    Calin A (1985) Ankylosing spondylitis. Clin Rheum Dis 11:41–60PubMedGoogle Scholar
  26. 26.
    Van der Linden SM, Valkenburg HA, Cats A (1984) Evaluation of the diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27:361–368PubMedCrossRefGoogle Scholar
  27. 27.
    Rudwaleit M, Jurik AG, Hermann KG et al (2009) Defining active sacroiliitis on magnetic resonance imaging (MRI) for classification of axial spondyloarthritis: a consensual approach by the ASAS/OMERA. Ann Rheum Dis 68:1520–1527 (Epub 2009 May 18)PubMedCrossRefGoogle Scholar
  28. 28.
    Jurinke C, van den Boom D, Cantor CR, Köster H (2002) Automated genotyping using the DNA MassArray technology. Methods Mol Biol 187:179–192PubMedGoogle Scholar
  29. 29.
    Ye S, Dhillon S, Ke X, Collins AR, Day IN (2001) An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Res 29:E88-8PubMedCrossRefGoogle Scholar
  30. 30.
    Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265PubMedCrossRefGoogle Scholar
  31. 31.
    Akaike H (1974) A new look at the statistical model identification. IEEE Trans Automat Control AC-19, pp 716–723Google Scholar
  32. 32.
    Purcell S, Neale B, Todd-Brown K et al (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575PubMedCrossRefGoogle Scholar
  33. 33.
    Benjamini Y, Hochberg Y (2000) The adaptive control of the false discovery rate in multiple hypotheses testing. J Behav Educ Statist 25:60–83Google Scholar
  34. 34.
    Purcell S, Cherny SS, Sham PC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150PubMedCrossRefGoogle Scholar
  35. 35.
    Nair RP, Duffin KC, Helms C et al (2009) Collaborative association study of psoriasis: genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 41:199–204 (Epub 2009 Jan 25)PubMedCrossRefGoogle Scholar
  36. 36.
    Duerr RH, Taylor KD, Brant SR et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463 (Epub 2006 Oct 26)PubMedCrossRefGoogle Scholar
  37. 37.
    Rahman P, Inman RD, Gladman DD, Reeve JP, Peddle L, Maksymowych WP (2008) Association of interleukin-23 receptor variants with ankylosing spondylitis. Arthritis Rheum 58:1020–1025PubMedCrossRefGoogle Scholar
  38. 38.
    Rueda B, Orozco G, Raya E et al (2008) The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis. Ann Rheum Dis 67:1451–1454PubMedCrossRefGoogle Scholar
  39. 39.
    Hollis-Moffatt JE, Merriman ME, Rodger RA et al (2009) Evidence for association of an interleukin 23 receptor variant independent of the R381Q variant with rheumatoid arthritis. Ann Rheum Dis 68:1340–1344PubMedCrossRefGoogle Scholar
  40. 40.
    Varade J, Ramón Lamas J, Rodríguez L et al (2009) IL23R and IL12B genes: susceptibility analysis in rheumatoid arthritis. Ann Rheum Dis 68:1230–1232PubMedCrossRefGoogle Scholar
  41. 41.
    Faragó B, Magyari L, Sáfrány E et al (2008) Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis. Ann Rheum Dis 67:248–250PubMedCrossRefGoogle Scholar
  42. 42.
    Safrany E, Hobor R, Jakab L et al (2010) Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients. Inflamm Res 59:159–164PubMedCrossRefGoogle Scholar
  43. 43.
    Orozco G, Rueda B, Robledo G, García A, Martín J (2007) Investigation of the IL23R gene in a Spanish rheumatoid arthritis cohort. Hum Immunol 68:681–684PubMedCrossRefGoogle Scholar
  44. 44.
    Park JH, Kim YJ, Park BL, Bae JS, Shin HD, Bae SC (2009) Lack of association between interleukin 23 receptor gene polymorphisms and rheumatoid arthritis susceptibility. Rheumatol Int 29:781–786PubMedCrossRefGoogle Scholar
  45. 45.
    Chang M, Saiki RK, Cantanese JJ et al (2008) The inflammatory disease-associated variants in IL12B and IL23R are not associated with rheumatoid arthritis. Arthritis Rheum 58:1877–1881PubMedCrossRefGoogle Scholar
  46. 46.
    Prots I, Skapenko A, Wendler J et al (2006) Association of the IL4R single-nucleotide polymorphism I50 V with rapidly erosive rheumatoid arthritis. Arthritis Rheum 54:1491–1500PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Maria Grazia Catanoso
    • 1
  • Luigi Boiardi
    • 1
  • Pierluigi Macchioni
    • 1
  • Paolo Garagnani
    • 2
  • Marco Sazzini
    • 2
  • Sara De Fanti
    • 2
  • Enrico Farnetti
    • 3
  • Bruno Casali
    • 3
  • Ilaria Chiarolanza
    • 1
  • Davide Nicoli
    • 3
  • Donata Luiselli
    • 2
  • Carlo Salvarani
    • 1
    Email author
  1. 1.Rheumatology UnitArcispedale S Maria Nuova, IRCCSReggio EmiliaItaly
  2. 2.Laboratory of Molecular Anthropology, Department of Experimental and Evolutionary BiologyUniversity of BolognaBolognaItaly
  3. 3.Laboratory of Molecular BiologyArcispedale Maria Nuova, IRCCSReggio EmiliaItaly

Personalised recommendations