This article is part of the supplement: 5th European Workshop on Immune-Mediated Inflammatory Diseases

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Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis

L M Diaz-Gallo1*, L Espino-Paisán2, K Fransen34, M Gómez-García5, S van Sommeren3, C Cardeña6, L Rodrigo7, J L Mendoza8, C Taxonera8, A Nieto9, G Alcain10, I Cueto10, M A López-Nevot11, N Bottini12, M L Barclay13, J B Crusius14, A A van Bodegraven15, C Wijmenga4, C Y Ponsioen16, R B Gearry17, R L Roberts18, R K Weersma3, E Urcelay2, T R Merriman18, B Z Alizadeh19 and J Martin1

  • * Corresponding author: L M Diaz-Gallo

Author Affiliations

1 Instituto de Parasitología y Biomedicina “López-Neyra”, CSIC, Granada, Spain

2 Dept. of Clinical Immunology, Hospital Clínico S. Carlos, Madrid, Spain

3 Dept. of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands

4 Dept. of Genetics, University Medical Center Groningen, Groningen, The Netherlands

5 Dept. of Gastroenterology, Hospital Virgen de las Nieves, Granada, Spain

6 Dept. of Gastroenterology, Hospital Clínico San Cecilio, Granada, Spain

7 Dept. of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain

8 Dept. of Gastroenterology, Hospital Universitario S. Carlos, Madrid, Spain

9 Dept. of Immunology, Hospital Puerta del Mar, Cádiz, Spain

10 Dept. of Gastroenterology, Hospital Virgen de la Victoria, Málaga, Spain

11 Dept. of Immunology, Hospital Virgen de las Nieves, Granada, Spain

12 Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA

13 Dept. of Medicine, University of Otago, Christchurch, New Zealand

14 Dept. of Pathology, VU University Medical Center, Amsterdam, The Netherlands

15 Dept. of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands

16 Dept. of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, The Netherlands

17 Dept. of Medicine, University of Otago, Christchurch, New Zealand

18 Biochemistry Dept., University of Otago, Dunedin, New Zealand

19 Unit of Genetic Epidemiology & Bioinformatics, Dept. of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands

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Journal of Translational Medicine 2010, 8(Suppl 1):P2  doi:10.1186/1479-5876-8-S1-P2

The electronic version of this article is the complete one and can be found online at:

Published:25 November 2010

© 2010 Diaz-Gallo et al; licensee BioMed Central Ltd.


The PTPN22 gene is an important risk factor for human autoimmunity. Two PTPN22 missense-SNPs, both with functional influence, the R620W (1858C>T, rs2476601) in exon 14 and the R263Q (788G>A, rs33996649) in exon 10 have been associated with autoimmune diseases [1-4].


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 re-evaluated the association of the R620W PTPN22 polymorphism with both diseases.

Patients and methods

A total of 1,677 UC patients, 1,903 CD patients and 3,107 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 and R620W PTPN22 polymorphisms. Meta-analysis was performed on 6977 CD, 5695 UC and 9254 controls to test the overall effect of the minor allele of R620W variant, and on the three Caucasian cohorts for the R263Q polymorphism.


The PTPN22 263Q loss-of-function variant showed an initial evidence of a significant association with UC in the Spanish cohort (p=0.026,OR=0.61,95%CI=0.39-0.95), which was confirmed in the meta-analysis (p=0.013pooled,OR=0.69,95%CI=0.51-0.93). In contrast, the 263Q allele showed no association to CD, (p=0.22pooled,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-06pooled, OR=0.81,95%CI=0.75-0.89) but not of UC (p=0.88pooled, 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 meanwhile the R620W was significantly related with CD. Our findings support the idea that the two major IBD phenotypes differ in some genetic components, and also in specific variants within a single gene, thus suggesting the involvement of different immunological mechanisms with a related nature.


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