Molecular Biology Reports

, Volume 39, Issue 8, pp 7861–7870 | Cite as

PTPN22 C1858T and the risk of psoriasis: a meta-analysis

  • Yu-Fu Chen
  • Jeffrey S. Chang


Psoriasis is a chronic autoimmune skin disease with both environmental and genetic risk factors. Previous studies of the association between psoriasis and PTPN22 C1858T (rs2476601), a gain of function variant associated with a stronger inhibitory effect of T-lymphocytes, have produced inconsistent results. The purpose of the current study is to evaluate the association between PTPN22 C1858T and psoriasis using meta-analysis to: (1) have a sufficient sample size for detecting a weak association; and (2) to explore the heterogeneity between studies. A meta-analysis based on random-effects model was performed with ten studies (3,334 psoriasis cases and 5,753 controls) identified from a literature search. A non-significantly positive association between psoriasis and the PTPN22 T1858 was observed [summary allelic odds ratio (OR) = 1.15, 95 % confidence interval (CI): 1.00–1.33] and the association appears stronger among subjects with psoriatic arthritis (summary allelic OR = 1.23, 95 % CI: 1.00–1.52). A null association between PTPN22 T1858 and early-onset psoriasis was observed (summary allelic OR = 1.08, 95 % CI: 0.92–1.28). The current analysis showed a non-significantly positive association between psoriasis and the PTPN22 T1858 allele, and the association appeared stronger among subjects with psoriatic arthritis. Future studies of psoriasis should incorporate gene-environment interaction in the analysis and pay attention to the heterogeneity of psoriasis cases and bias associated with population stratification.


Psoriasis Psoriatic arthritis PTPN22 Meta-analysis 

Supplementary material

11033_2012_1630_MOESM1_ESM.doc (92 kb)
Supplementary material 1 (DOC 92 kb)


  1. 1.
    Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509PubMedCrossRefGoogle Scholar
  2. 2.
    Gudjonsson JE, Elder JT (2007) Psoriasis: epidemiology. Clin Dermatol 25:535–546PubMedCrossRefGoogle Scholar
  3. 3.
    Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:J314–J321PubMedCrossRefGoogle Scholar
  4. 4.
    Ibrahim G, Waxman R, Helliwell PS (2009) The prevalence of psoriatic arthritis in people with psoriasis. Arthritis Rheum 61:1373–1378PubMedCrossRefGoogle Scholar
  5. 5.
    Gelfand JM, Gladman DD, Mease PJ, Smith N, Margolis DJ, Nijsten T et al (2005) Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol 53:573PubMedCrossRefGoogle Scholar
  6. 6.
    Rahman P, Elder JT (2005) Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 64 Suppl 2: ii37–ii39; discussion ii40–ii31Google Scholar
  7. 7.
    Chandran V, Schentag CT, Brockbank JE, Pellett FJ, Shanmugarajah S, Toloza SM et al (2009) Familial aggregation of psoriatic arthritis. Ann Rheum Dis 68:664–667PubMedCrossRefGoogle Scholar
  8. 8.
    Elder JT, Nair RP, Guo SW, Henseler T, Christophers E, Voorhees JJ (1994) The genetics of psoriasis. Arch Dermatol 130:216–224PubMedCrossRefGoogle Scholar
  9. 9.
    Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP (2011) Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 585(23):3689–3698PubMedCrossRefGoogle Scholar
  10. 10.
    Vang T, Congia M, Macis MD, Musumeci L, Orru V, Zavattari P et al (2005) Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 37:1317–1319PubMedCrossRefGoogle Scholar
  11. 11.
    Arechiga AF, Habib T, He Y, Zhang X, Zhang ZY, Funk A et al (2009) Cutting edge: the PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 182:3343–3347PubMedCrossRefGoogle Scholar
  12. 12.
    Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M et al (2005) Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 76:561–571PubMedCrossRefGoogle Scholar
  13. 13.
    Hinks A, Barton A, John S, Bruce I, Hawkins C, Griffiths CE et al (2005) Association between the PTPN22 gene and rheumatoid arthritis and juvenile idiopathic arthritis in a UK population: further support that PTPN22 is an autoimmunity gene. Arthritis Rheum 52:1694–1699PubMedCrossRefGoogle Scholar
  14. 14.
    Butt C, Peddle L, Greenwood C, Hamilton S, Gladman D, Rahman P (2006) Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case–control study. Arthritis Res Ther 8:R27PubMedCrossRefGoogle Scholar
  15. 15.
    Huffmeier U, Steffens M, Burkhardt H, Lascorz J, Schurmeier-Horst F, Stander M et al (2006) Evidence for susceptibility determinant(s) to psoriasis vulgaris in or near PTPN22 in German patients. J Med Genet 43:517–522PubMedCrossRefGoogle Scholar
  16. 16.
    Huffmeier U, Reis A, Steffens M, Lascorz J, Bohm B, Lohmann J et al (2006) Male restricted genetic association of variant R620W in PTPN22 with psoriatic arthritis. J Invest Dermatol 126:932–935PubMedCrossRefGoogle Scholar
  17. 17.
    Smith RL, Warren RB, Eyre S, Ke X, Young HS, Allen M et al (2008) Polymorphisms in the PTPN22 region are associated with psoriasis of early onset. Br J Dermatol 158:962–968PubMedCrossRefGoogle Scholar
  18. 18.
    Zervou MI, Castro-Giner F, Sidiropoulos P, Boumpas DT, Tosca AD, Krueger-Krasagakis S (2010) The protein tyrosine phosphatase, non-receptor type 22 R620W polymorphism does not confer susceptibility to psoriasis in the genetic homogeneous population of Crete. Genet Test Mol Biomarkers 14:107–111PubMedCrossRefGoogle Scholar
  19. 19.
    Juneblad K, Johansson M, Rantapaa-Dahlqvist S, Alenius GM (2011) Association between the PTPN22 + 1858 C/T polymorphism and psoriatic arthritis. Arthritis Res Ther 13:R45PubMedCrossRefGoogle Scholar
  20. 20.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  21. 21.
    Bradburn MJ (2004) Updated and new commands for meta-analysis in Stata. Available: Accessed 23 April 2011
  22. 22.
    Lewis S, Clarke M (2001) Forest plots: trying to see the wood and the trees. BMJ 322:1479–1480PubMedCrossRefGoogle Scholar
  23. 23.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560PubMedCrossRefGoogle Scholar
  24. 24.
    Sterne JAC, Egger M, Smith GD (2005) Investigating and dealing with publication and other biases. In: Egger M, Smith GD, Altman DG (eds) Systematic reviews in health: care meta-analysis context. BMJ Books, London, pp 285–312Google Scholar
  25. 25.
    Henseler T, Christophers E (1985) Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 13:450–456PubMedCrossRefGoogle Scholar
  26. 26.
    Naldi L, Mercuri SR (2009) Smoking and psoriasis: from epidemiology to pathomechanisms. J Invest Dermatol 129:2741–2743PubMedCrossRefGoogle Scholar
  27. 27.
    Costenbader KH, Chang SC, De Vivo I, Plenge R, Karlson EW (2008) Genetic polymorphisms in PTPN22, PADI-4, and CTLA-4 and risk for rheumatoid arthritis in two longitudinal cohort studies: evidence of gene-environment interactions with heavy cigarette smoking. Arthritis Res Ther 10:R52PubMedCrossRefGoogle Scholar
  28. 28.
    Thomas DC, Witte JS (2002) Point: population stratification: a problem for case–control studies of candidate-gene associations? Cancer Epidemiol Biomarkers Prev 11:505–512PubMedGoogle Scholar
  29. 29.
    Vang T, Miletic AV, Arimura Y, Tautz L, Rickert RC, Mustelin T (2008) Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol 26:29–55PubMedCrossRefGoogle Scholar
  30. 30.
    Nistor I, Nair RP, Stuart P, Hiremagalore R, Thompson RA, Jenisch S et al (2005) Protein tyrosine phosphatase gene PTPN22 polymorphism in psoriasis: lack of evidence for association. J Invest Dermatol 125:395–396PubMedGoogle Scholar
  31. 31.
    Price AL, Butler J, Patterson N, Capelli C, Pascali VL, Scarnicci F et al (2008) Discerning the ancestry of European Americans in genetic association studies. PLoS Genet 4:e236PubMedCrossRefGoogle Scholar
  32. 32.
    Li Y, Liao W, Chang M, Schrodi SJ, Bui N, Catanese JJ et al (2009) Further genetic evidence for three psoriasis-risk genes: ADAM33, CDKAL1, and PTPN22. J Invest Dermatol 129:629–634PubMedCrossRefGoogle Scholar
  33. 33.
    Carlton VE, Hu X, Chokkalingam AP, Schrodi SJ, Brandon R, Alexander HC et al (2005) PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am J Hum Genet 77:567–581PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of DermatologyShow-Chwan Memorial HospitalChanghuaTaiwan
  2. 2.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan

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