Abstract
Purpose
Our aims were to evaluate protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene polymorphisms in ulcerative colitis (UC) and explore PTPN22 mRNA levels in colonic biopsies of UC patients in central China.
Methods
A total of 165 Chinese UC patients and 300 healthy controls were enrolled in this study. PTPN22 −1123G/C, +1858C/T, and +788G/A polymorphisms were genotyped by PCR-restriction fragment length polymorphism method. PTPN22 mRNA expressions in colonic biopsies and serum C-reactive protein (CRP) levels were determined by quantitative PCR and immunonephelometry, respectively.
Results
The frequency of C carrier was higher in UC patients than in healthy controls (66.7 vs. 53.3 %, P = 0.005, odds ratios = 1.75, 95 % CI 1.18–2.60) and associated with extensive colitis (P = 0.029). PTPN22 mRNA levels were elevated in UC patients than in healthy controls (P < 0.001). Among UC patients, PTPN22 mRNA expression levels were higher in biopsies of inflamed colonic tissue compared with noninflamed tissue (P < 0.001) and were correlated with CRP levels (r = 0.578, P < 0.001). PTPN22 mRNA expression levels were elevated in extensive colitis compared to proctitis (P = 0.008) and to left-sided colitis (P = 0.029) and were higher in moderate and severe disease than in mild disease (P = 0.005).
Conclusions
Our study showed the potential association between PTPN22 −1123G/C polymorphism and UC in central China. PTPN22 mRNA levels were highly expressed in UC, especially in active disease, and were correlated with CRP levels, disease location, and disease severity in UC patients.
Similar content being viewed by others
References
Xavier RJ, Podolsky DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448:427–434
Behrens TW (2011) Lyp breakdown and autoimmunity. Nat Genet 43:821–822
Zhang J, Zahir N, Jiang Q et al (2011) The autoimmune disease-associated PTPN22 variant promotes calpain-mediated LYP/Pep degradation associated with lymphocyte and dendritic cell hyperresponsiveness. Nat Genet 43:902–907
Cloutier JF, Veillette A (1999) Cooperative inhibition of T-cell antigen receptor signaling by a complex between a kinase and a phosphatase. J Exp Med 189:111–121
Wu S, Bottini M, Rickert RC et al (2009) In silico screening for PTPN22 inhibitors: active hits from an inactive phosphatase conformation. ChemMedChem 4:440–444
Xie Y, Liu Y, Gong G et al (2008) Discovery of a novel submicromolar inhibitor of the lymphoid specific tyrosine phosphatase. Bioorg Med Chem Lett 18:2840–2844
Stanford SM, Mustelin TM, Bottini N (2010) Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases. Semin Immunopathol 32:127–136
Dultz G, Matheis N, Dittmar M et al (2009) The protein tyrosine phosphatase non-receptor type 22 C1858T polymorphism is a joint susceptibility locus for immunthyroiditis and autoimmune diabetes. Thyroid 19:143–148
Bottini N, Vang T, Cucca F et al (2006) Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol 18:207–213
Chung SA, Criswell LA (2007) PTPN22: its role in SLE and autoimmunity. Autoimmunity 40:582–590
Diaz-Gallo LM, Espino-Paisán L, Fransen K et al (2011) Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis 17:2287–2294
Kawasaki E, Awata T, Ikegami H et al (2006) Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations. Am J Med Genet A 140:586–593
Liu F, Liu J, Zheng TS et al (2012) The −1123G>C variant of PTPN22 gene promoter is associated with latent autoimmune diabetes in adult Chinese Hans. Cell Biochem Biophys 62:273–279
Huang JJ, Qiu YR, Li HX et al (2012) A PTPN22 promoter polymorphism −1123G>C is associated with RA pathogenesis in Chinese. Rheumatol Int 32:767–771
Feng X, Li YZ, Zhang Y et al (2010) Association of the PTPN22 gene (−1123G>C) polymorphism with rheumatoid arthritis in Chinese patients. Tissue Antigens 76:297–300
Orrú V, Tsai SJ, Rueda B et al (2009) A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Hum Mol Genet 18:569–579
Rodríguez-Rodríguez L, Taib WR, Topless R et al (2011) The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case–control samples. Arthritis Rheum 63:365–372
Lennard-Jones JE (1989) Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl 170:2–6
Satsangi J, Silverberg MS, Vermeire S et al (2006) The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55:749–753
Truelove SC, Witts LJ (1955) Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J 2:1041–1048
Chang HH, Tai TS, Lu B et al (2012) PTPN22.6, a dominant negative isoform of PTPN22 and potential biomarker of rheumatoid arthritis. PLoS One 7:e33067
Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108
Inoue A, Takahashi KA, Arai Y et al (2006) The therapeutic effects of basic fibroblast growth factor contained in gelatin hydrogel microspheres on experimental osteoarthritis in the rabbit knee. Arthritis Rheum 54:264–270
Oikonomou KA, Kapsoritakis AN, Kapsoritaki AI et al (2011) Angiogenin, angiopoietin-1, angiopoietin-2, and endostatin serum levels in inflammatory bowel disease. Inflamm Bowel Dis 17:963–970
Viken MK, Olsson M, Flåm ST et al (2007) The PTPN22 promoter polymorphism −1123G>C association cannot be distinguished from the 1858C>T association in a Norwegian rheumatoid arthritis material. Tissue Antigens 70:190–197
Jostins L, Ripke S, Weersma RK et al (2012) Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124
Mori M, Yamada R, Kobayashi K et al (2005) Ethnic differences in allele frequency of autoimmune-disease-associated SNPs. J Hum Genet 50:264–266
Ronninger M, Guo Y, Shchetynsky K et al (2012) The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls. Genome Med 4:2
Wu J, Katrekar A, Honigberg LA et al (2006) Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem 281:11002–11010
Jüliger S, Bongartz M, Luty AJ et al (2003) Functional analysis of a promoter variant of the gene encoding the interferon-gamma receptor chain I. Immunogenetics 54:675–680
Acknowledgments
This project was supported by grants from the Bureau of Public Health of Wuhan (WX12C34).
Conflict of interest
The authors declare that they have no competing interests.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Chen, Z., Zhang, H., Xia, B. et al. Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis. Int J Colorectal Dis 28, 1351–1358 (2013). https://doi.org/10.1007/s00384-013-1671-3
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00384-013-1671-3