These authors contributed equally to this work.
Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis†
Article first published online: 1 FEB 2011
Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 17, Issue 11, pages 2287–2294, November 2011
How to Cite
Diaz-Gallo, L.-M., Espino-Paisán, L., Fransen, K., Gómez-García, M., van Sommeren, S., Cardeña, C., Rodrigo, L., Mendoza, J. L., Taxonera, C., Nieto, A., Alcain, G., Cueto, I., López-Nevot, M. A., Bottini, N., Barclay, M. L., Crusius, J. B., van Bodegraven, A. A., Wijmenga, C., Ponsioen, C. Y., Gearry, R. B., Roberts, R. L., Weersma, R. K., Urcelay, E., Merriman, T. R., Alizadeh, B. Z. and Martin, J. (2011), Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis. Inflamm Bowel Dis, 17: 2287–2294. doi: 10.1002/ibd.21630
Supported by Plan Nacional de I+D, grant: SAF06-00398), Junta de Andalucía, grant: CTS-1180 and FIS PI08/1676. Health Research Council (HRC) of NZ, grant: 08/075C. R.L.R. is the recipient of a Sir Charles Hercus Health Research Fellowship (HRC). Banco Nacional de ADN (University of Salamanca, Spain) supplied part of the control DNA samples. L.M.D.G. was supported by the “Ayudas Predoctorales de Formación en Investigación en Salud (PFIS – FI09/00544)” and COLFUTURO, B.Z.A. was supported by grants from the Netherlands Organization for Health Research and Development (ZonMw, grant number 016.096.121).
- Issue published online: 10 OCT 2011
- Article first published online: 1 FEB 2011
- Manuscript Accepted: 8 DEC 2010
- Manuscript Received: 1 DEC 2010
- protein tyrosine phosphatase;
- nonreceptor type 22 (PTPN22) gene;
- inflammatory bowel disease (IBD);
- ulcerative colitis (UC);
- Crohn's disease (CD)
The PTPN22 gene is an important risk factor for human autoimmunity. The aim of this study was to evaluate for the first time the role of the R263Q PTPN22 polymorphism in ulcerative colitis (UC) and Crohn's disease (CD), and to reevaluate the association of the R620W PTPN22 polymorphism with both diseases.
A total of 1677 UC patients, 1903 CD patients, and 3111 healthy controls from an initial case–control set of Spanish Caucasian ancestry and two independent sample sets of European ancestry (Dutch and New Zealand) were included in the study. Genotyping was performed using TaqMan SNP assays for the R263Q (rs33996649) and R620W (rs2476601) PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD patients, 5695 UC patients, and 9254 controls to test the overall effect of the minor allele of R620W and R263Q polymorphisms.
The PTPN22 263Q loss-of-function variant showed initial evidence of association with UC in the Spanish cohort (P = 0.026, odds ratio [OR] = 0.61, 95% confidence interval [CI]: 0.39–0.95), which was confirmed in the meta-analysis (P = 0.013 pooled, OR = 0.69, 95% CI: 0.51–0.93). In contrast, the 263Q allele showed no association with CD (P = 0.22 pooled, OR = 1.16, 95% CI: 0.91–1.47). We found in the pooled analysis that the PTPN22 620W gain-of-function variant was associated with reduced risk of CD (P = 7.4E-06 pooled OR = 0.81, 95% CI: 0.75–0.89) but not of UC (P = 0.88 pooled, OR = 0.98, 95% CI: 0.85–1.15).
Our data suggest that two autoimmunity-associated polymorphisms of the PTPN22 gene are differentially associated with CD and UC. The R263Q polymorphism only associated with UC, whereas the R620W was significantly associated with only CD. (Inflamm Bowel Dis 2011;)