2 páginas.-- Póster presentado al 5º European Workshop on Immune-Mediated Inflammatory Diseases celebrado en Sitges (Barcelona) dxel 1 al 3 de Diciembre de 2010.-- et al.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].Peer reviewe

A A van Bodegraven

A Nieto

B Z Alizadeh

C Cardeña

C Taxonera

C Wijmenga

C Y Ponsioen

E Urcelay

G Alcain

I Cueto

J B Crusius

J L Mendoza

J Martin

K Fransen

L Espino-Paisán

L M Diaz-Gallo

L Rodrigo

M A López-Nevot

M Gómez-García

M L Barclay

N Bottini

R B Gearry

R K Weersma

R L Roberts

S van Sommeren

SM Stanford

T R Merriman

V Orru

English

PubMed

Crossref

Journal of Translational Medicine

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

Weersma R K

Roberts R L

Gearry R B

Ponsioen C Y

Wijmenga C

van Bodegraven A A

Crusius J B

Barclay M L

Bottini N

López-Nevot M A

Cueto I

Nieto A

Alcain G

Taxonera C

Mendoza J L

Rodrigo L

Cardeña C

van Sommeren S

Gómez-García M

Fransen K

Espino-Paisán L

Diaz-Gallo L M

Urcelay E

Merriman T R

Alizadeh B Z

Martin J

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Differential association of two <it>PTPN22</it> coding variants with Crohn’s disease and ulcerative colitis

Díaz-Gallo, L. M.

Gómez-García, M.

Mendoza, Juan L.

Taxonera, Carlos

Nieto, M. Ángela

López-Nevot, Miguel-Ángel

Alizadeh, B. Z.

Martín, J.

Digital.CSIC

POSTER PRESENTATION Open AccessDifferential association of two PTPN22 codingvariants with Crohn’s disease and ulcerative colitisL M Diaz-Gallo1*, L Espino-Paisán2, K Fransen3,4, 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, J Martin1From 5th European Workshop on Immune-Mediated Inflammatory DiseasesSitges-Barcelona, Spain. 1-3 December 2010IntroductionThe PTPN22 gene is an important risk factor for humanautoimmunity. Two PTPN22 missense-SNPs, both withfunctional influence, the R620W (1858C>T, rs2476601) inexon 14 and the R263Q (788G>A, rs33996649) in exon 10have been associated with autoimmune diseases [1-4].AimThe aim of this study was to evaluate for the first time therole of the R263Q PTPN22 polymorphism in ulcerativecolitis (UC) and Crohn’s disease (CD), and re-evaluatedthe association of the R620W PTPN22 polymorphismwith both diseases.Patients and methodsA total of 1,677 UC patients, 1,903 CD patients and 3,107healthy controls, from an initial case-control set of Span-ish Caucasian ancestry and two independent sample setsof European ancestry (Dutch and New Zealand), wereincluded in the study. Genotyping was performed usingTaqMan SNP assays for the R263Q and R620W PTPN22polymorphisms. Meta-analysis was performed on 6977CD, 5695 UC and 9254 controls to test the overall effectof the minor allele of R620W variant, and on the threeCaucasian cohorts for the R263Q polymorphism.ResultsThe PTPN22 263Q loss-of-function variant showed aninitial evidence of a significant association with UC in theSpanish 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 alleleshowed no association to CD, (p=0.22pooled,OR=1.16,95%CI=0.91-1.47). We found in the pooled analysis that thePTPN22 620W gain-of-function variant was associatedwith 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).ConclusionOur data suggest that two autoimmunity-associatedpolymorphisms of the PTPN22 gene are differentiallyassociated with CD and UC. The R263Q polymorphismonly associated with UC meanwhile the R620W was sig-nificantly related with CD. Our findings support theidea that the two major IBD phenotypes differ in somegenetic components, and also in specific variants withina single gene, thus suggesting the involvement of differ-ent immunological mechanisms with a related nature.Author details1Instituto de Parasitología y Biomedicina “López-Neyra”, CSIC, Granada, Spain.2Dept. of Clinical Immunology, Hospital Clínico S. Carlos, Madrid, Spain.3Dept. of Gastroenterology and Hepatology, University Medical CenterGroningen, Groningen, The Netherlands. 4Dept. of Genetics, UniversityMedical Center Groningen, Groningen, The Netherlands. 5Dept. ofGastroenterology, Hospital Virgen de las Nieves, Granada, Spain. 6Dept. ofGastroenterology, Hospital Clínico San Cecilio, Granada, Spain. 7Dept. ofGastroenterology, Hospital Central de Asturias, Oviedo, Spain. 8Dept. ofGastroenterology, Hospital Universitario S. Carlos, Madrid, Spain. 9Dept. ofImmunology, Hospital Puerta del Mar, Cádiz, Spain. 10Dept. ofGastroenterology, Hospital Virgen de la Victoria, Málaga, Spain. 11Dept. ofImmunology, Hospital Virgen de las Nieves, Granada, Spain. 12Division of CellBiology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.13Dept. of Medicine, University of Otago, Christchurch, New Zealand. 14Dept.of Pathology, VU University Medical Center, Amsterdam, The Netherlands.15Dept. of Gastroenterology, VU University Medical Center, Amsterdam, TheNetherlands. 16Dept. of Gastroenterology and Hepatology, Academic MedicalCenter Amsterdam, The Netherlands. 17Dept. of Medicine, University of1Instituto de Parasitología y Biomedicina “López-Neyra”, CSIC, Granada, SpainFull list of author information is available at the end of the articleDiaz-Gallo et al. Journal of Translational Medicine 2010, 8(Suppl 1):P2http://www.translational-medicine.com/content/8/S1/P2© 2010 Diaz-Gallo et al; licensee BioMed Central Ltd.Otago, Christchurch, New Zealand. 18Biochemistry Dept., University of Otago,Dunedin, New Zealand. 19Unit of Genetic Epidemiology & Bioinformatics,Dept. of Epidemiology, University Medical Center Groningen, Groningen, TheNetherlands.Published: 25 November 2010References1. Stanford SM, Mustelin TM, Bottini N: Lymphoid tyrosine phosphatase andautoimmunity: human genetics rediscovers tyrosine phosphatases. SeminImmunopathol 2010, 32(2):127-36.2. Bottini N, et al: A functional variant of lymphoid tyrosine phosphatase isassociated with type I diabetes. Nat Genet 2004, 36(4):337-8.3. Bottini N, et al: Role of PTPN22 in type 1 diabetes and otherautoimmune diseases. Semin Immunol 2006, 18(4):207-13.4. Orru V, et al: A loss-of-function variant of PTPN22 is associated withreduced risk of systemic lupus erythematosus. Hum Mol Genet 2009,18(3):569-79.doi:10.1186/1479-5876-8-S1-P2Cite this article as: Diaz-Gallo et al.: Differential association of twoPTPN22 coding variants with Crohn’s disease and ulcerative colitis.Journal of Translational Medicine 2010 8(Suppl 1):P2.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitDiaz-Gallo et al. Journal of Translational Medicine 2010, 8(Suppl 1):P2http://www.translational-medicine.com/content/8/S1/P2Page 2 of 2

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet

A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Hum Mol Genet

et al: Role of PTPN22 in type 1 diabetes and other autoimmune diseases. Semin Immunol

Lymphoid tyrosine phosphatase and autoimmunity: human genetics rediscovers tyrosine phosphatases. Semin Immunopathol

Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

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

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