TY - JOUR
T1 - Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis
AU - Diaz-Gallo, Lina-Marcela
AU - Espino-Paisán, Laura
AU - Fransen, Karin
AU - Gómez-García, María
AU - van Sommeren, Suzanne
AU - Cardeña, Carlos
AU - Rodrigo, Luis
AU - Mendoza, Juan Luis
AU - Taxonera, Carlos
AU - Nieto, Antonio
AU - Alcain, Guillermo
AU - Cueto, Ignacio
AU - López-Nevot, Miguel A.
AU - Bottini, Nunzio
AU - Barclay, Murray L.
AU - Crusius, J. Bart
AU - van Bodegraven, Adriaan A.
AU - Wijmenga, Cisca
AU - Ponsioen, Cyriel Y.
AU - Gearry, Richard B.
AU - Roberts, Rebecca L.
AU - Weersma, Rinse K.
AU - Urcelay, Elena
AU - Merriman, Tony R.
AU - Alizadeh, Behrooz Z.
AU - Martin, Javier
AU - Mendoza, JL
AU - Alizadeh, BZ
PY - 2011
Y1 - 2011
N2 - 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
AB - 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
U2 - https://doi.org/10.1002/ibd.21630
DO - https://doi.org/10.1002/ibd.21630
M3 - Article
C2 - 21287672
SN - 1078-0998
VL - 17
SP - 2287
EP - 2294
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 11
ER -