Abstract
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.
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References
Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361:496–509
Gudjonsson JE, Elder JT (2007) Psoriasis: epidemiology. Clin Dermatol 25:535–546
Chandran V, Raychaudhuri SP (2010) Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 34:J314–J321
Ibrahim G, Waxman R, Helliwell PS (2009) The prevalence of psoriatic arthritis in people with psoriasis. Arthritis Rheum 61:1373–1378
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 53:573
Rahman P, Elder JT (2005) Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 64 Suppl 2: ii37–ii39; discussion ii40–ii31
Chandran V, Schentag CT, Brockbank JE, Pellett FJ, Shanmugarajah S, Toloza SM et al (2009) Familial aggregation of psoriatic arthritis. Ann Rheum Dis 68:664–667
Elder JT, Nair RP, Guo SW, Henseler T, Christophers E, Voorhees JJ (1994) The genetics of psoriasis. Arch Dermatol 130:216–224
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):3689–3698
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 37:1317–1319
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 182:3343–3347
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 76:561–571
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 52:1694–1699
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:R27
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 43:517–522
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 126:932–935
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 158:962–968
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 14:107–111
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:R45
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Bradburn MJ (2004) Updated and new commands for meta-analysis in Stata. Available: http://www.medepi.net/meta/software/Bradburn_metan_updates.pdf. Accessed 23 April 2011
Lewis S, Clarke M (2001) Forest plots: trying to see the wood and the trees. BMJ 322:1479–1480
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560
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 285–312
Henseler T, Christophers E (1985) Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J Am Acad Dermatol 13:450–456
Naldi L, Mercuri SR (2009) Smoking and psoriasis: from epidemiology to pathomechanisms. J Invest Dermatol 129:2741–2743
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:R52
Thomas DC, Witte JS (2002) Point: population stratification: a problem for case–control studies of candidate-gene associations? Cancer Epidemiol Biomarkers Prev 11:505–512
Vang T, Miletic AV, Arimura Y, Tautz L, Rickert RC, Mustelin T (2008) Protein tyrosine phosphatases in autoimmunity. Annu Rev Immunol 26:29–55
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 125:395–396
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:e236
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 129:629–634
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 77:567–581
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Chen, YF., Chang, J.S. PTPN22 C1858T and the risk of psoriasis: a meta-analysis. Mol Biol Rep 39, 7861–7870 (2012). https://doi.org/10.1007/s11033-012-1630-z
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DOI: https://doi.org/10.1007/s11033-012-1630-z