Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis

Abstract

Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Nestle FO, Kaplan DH, Barker J . Psoriasis. N Engl J Med 2009; 361: 496–509.

    Article  CAS  Google Scholar 

  2. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet 2009; 41: 199–204.

    Article  CAS  Google Scholar 

  3. Ellinghaus E, Ellinghaus D, Stuart PE, Nair RP, Debrus S, Raelson JV, et al. Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet 2010; 42: 991–995.

    Article  CAS  Google Scholar 

  4. Huffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E, Korendowych E, et al. Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nat Genet 2010; 42: 996–999.

    Article  Google Scholar 

  5. Strange A, Capon F, Spencer CC, Knight J, Weale ME, Allen MH, et al. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat Genet 2010; 42: 985–990.

    Article  CAS  Google Scholar 

  6. Sun LD, Cheng H, Wang ZX, Zhang AP, Wang PG, Xu JH, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 2010; 42: 1005–1009.

    Article  CAS  Google Scholar 

  7. Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 2010; 42: 1000–1004.

    Article  CAS  Google Scholar 

  8. Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, et al. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet 2012; 44: 1341–1348.

    Article  CAS  Google Scholar 

  9. Feldmann M . Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol 2002; 2: 364–371.

    Article  CAS  Google Scholar 

  10. Chaudhari U, Romano P, Mulcahy LD, Dooley LT, Baker DG, Gottlieb AB . Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomised trial. Lancet 2001; 357: 1842–1847.

    Article  CAS  Google Scholar 

  11. Prieto-Perez R, Cabaleiro T, Dauden E, Abad-Santos F . Gene polymorphisms that can predict response to anti-TNF therapy in patients with psoriasis and related autoimmune diseases. Pharmacogenom J 2013; 13: 297–305.

    Article  CAS  Google Scholar 

  12. Mahil SK, Arkir Z, Richards G, Lewis CM, Barker JN, Smith CH . Predicting treatment response in psoriasis using serum levels of adalimumab and etanercept: a single-centre, cohort study. Br J Dermatol 2013; 169: 306–313.

    Article  CAS  Google Scholar 

  13. Smith CH, Anstey AV, Barker JN, Burden AD, Chalmers RJ, Chandler DA, et al. British Association of Dermatologists' guidelines for biologic interventions for psoriasis 2009. Br J Dermatol 2009 161: 987–1019.

  14. Lowes MA, Bowcock AM, Krueger JG . Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866–873.

    Article  CAS  Google Scholar 

  15. Julia A, Tortosa R, Hernanz JM, Canete JD, Fonseca E, Ferrandiz C, et al. Risk variants for psoriasis vulgaris in a large case–control collection and association with clinical subphenotypes. Hum Mol Genet 2012; 21: 4549–4557.

    Article  CAS  Google Scholar 

  16. Tejasvi T, Stuart PE, Chandran V, Voorhees JJ, Gladman DD, Rahman P, et al. TNFAIP3 gene polymorphisms are associated with response to TNF blockade in psoriasis. J Invest Dermatol 2012; 132: 593–600.

    Article  CAS  Google Scholar 

  17. Krintel SB, Palermo G, Johansen JS, Germer S, Essioux L, Benayed R, et al. Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFalpha inhibitors in patients with rheumatoid arthritis. Pharmacogenet Genom 2012; 22: 577–589.

    Article  CAS  Google Scholar 

  18. Acosta-Colman I, Palau N, Tornero J, Fernandez-Nebro A, Blanco F, Gonzalez-Alvaro I, et al. GWAS replication study confirms the association of PDE3A-SLCO1C1 with anti-TNF therapy response in rheumatoid arthritis. Pharmacogenomics 2013; 14: 727–734.

    Article  CAS  Google Scholar 

  19. Fredriksson T, Pettersson U . Severe psoriasis—oral therapy with a new retinoid. Dermatologica 1978; 157: 238–244.

    Article  CAS  Google Scholar 

  20. Julia M, Guilabert A, Lozano F, Suarez-Casasus B, Moreno N, Carrascosa JM, et al. The role of Fcgamma receptor polymorphisms in the response to anti-tumor necrosis factor therapy in psoriasis. A pharmacogenetic study. JAMA Dermatol 2013; 149: 1033–1039.

    Article  CAS  Google Scholar 

  21. Team RC (2013). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria, 2009.

  22. Lappalainen T, Sammeth M, Friedlander MR, t Hoen PA, Monlong J, Rivas MA, et al. Transcriptome and genome sequencing uncovers functional variation in humans. Nature 2013; 501: 506–511.

    Article  CAS  Google Scholar 

  23. Schafer P . Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol 2012; 83: 1583–1590.

    Article  CAS  Google Scholar 

  24. Schiffer R, Neis M, Holler D, Rodriguez F, Geier A, Gartung C, et al. Active influx transport is mediated by members of the organic anion transporting polypeptide family in human epidermal keratinocytes. J Invest Dermatol 2003; 120: 285–291.

    Article  CAS  Google Scholar 

  25. Ramsey LB, Panetta JC, Smith C, Yang W, Fan Y, Winick NJ, et al. Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood 2013; 121: 898–904.

    Article  CAS  Google Scholar 

  26. Carrascosa JM, Rocamora V, Fernandez-Torres RM, Jimenez-Puya R, Moreno JC, Coll-Puigserver N, et al. Obesity and psoriasis: inflammatory nature of obesity, relationship between psoriasis and obesity, and therapeutic implications. Acta Dermosifiliogr 2014; 105: 31–44.

    Article  CAS  Google Scholar 

  27. Puig L . Obesity and psoriasis: body weight and body mass index influence the response to biological treatment. J Eur Acad Dermatol Venereol 2011; 25: 1007–1011.

    Article  CAS  Google Scholar 

  28. Carrascosa JM, Vilavella M, Garcia-Doval I, Carretero G, Vanaclocha F, Dauden E, et al. Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry. J Eur Acad Dermatol Venereol 2013; 28: 907–914.

    Article  Google Scholar 

  29. Fransen J, van Riel PL . The disease activity score and the EULAR response criteria. Rheum Dis Clin N Am 2009; 35: 745–757, vii-viii.

    Article  Google Scholar 

  30. Bowcock AM, Krueger JG . Getting under the skin: the immunogenetics of psoriasis. Nat Rev Immunol 2005; 5: 699–711.

    Article  CAS  Google Scholar 

  31. Sfikakis PP, Iliopoulos A, Elezoglou A, Kittas C, Stratigos A . Psoriasis induced by anti-tumor necrosis factor therapy: a paradoxical adverse reaction. Arthritis Rheum 2005; 52: 2513–2518.

    Article  CAS  Google Scholar 

  32. Harrison MJ, Dixon WG, Watson KD, King Y, Groves R, Hyrich KL, et al. Rates of new-onset psoriasis in patients with rheumatoid arthritis receiving anti-tumour necrosis factor alpha therapy: results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2009; 68: 209–215.

    Article  CAS  Google Scholar 

  33. Moroi R, Endo K, Kinouchi Y, Shiga H, Kakuta Y, Kuroha M, et al. FCGR3A-158 polymorphism influences the biological response to infliximab in Crohn's disease through affecting the ADCC activity. Immunogenetics 2013; 65: 265–271.

    Article  CAS  Google Scholar 

  34. Ramirez J, Fernandez-Sueiro JL, Lopez-Mejias R, Montilla C, Arias M, Moll C, et al. FCGR2A/CD32A and FCGR3A/CD16A variants and EULAR response to tumor necrosis factor-alpha blockers in psoriatic arthritis: a longitudinal study with 6 months of followup. J Rheumatol 2012; 39: 1035–1041.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Spanish Ministry of Economy and Competitiveness Strategic Project grants (PSE-010000-2006-6, IPT-010000-2010-36).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Marsal.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Julià, A., Ferrándiz, C., Dauden, E. et al. Association of the PDE3A-SLCO1C1 locus with the response to anti-TNF agents in psoriasis. Pharmacogenomics J 15, 322–325 (2015). https://doi.org/10.1038/tpj.2014.71

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/tpj.2014.71

This article is cited by

Search

Quick links