title: Differential association of two PTPN22 coding variants with Crohn's disease and ulcerative colitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
authors.forename: Lina-Marcela
authors.initials: LM
authors.lastname: Diaz-Gallo
authors.forename: Laura
authors.initials: L
authors.lastname: Espino-Paisán
authors.forename: Karin
authors.initials: K
authors.lastname: Fransen
authors.forename: María
authors.initials: M
authors.lastname: Gómez-García
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Sommeren
authors.forename: Carlos
authors.initials: C
authors.lastname: Cardeña
authors.forename: Luis
authors.initials: L
authors.lastname: Rodrigo
authors.forename: Juan Luis
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.forename: Antonio
authors.initials: A
authors.lastname: Nieto
authors.forename: Guillermo
authors.initials: G
authors.lastname: Alcain
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cueto
authors.forename: Miguel A
authors.initials: MA
authors.lastname: López-Nevot
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Murray L
authors.initials: ML
authors.lastname: Barclay
authors.forename: J Bart
authors.initials: JB
authors.lastname: Crusius
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Bodegraven
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
authors.forename: Richard B
authors.initials: RB
authors.lastname: Gearry
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Roberts
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.forename: Behrooz Z
authors.initials: BZ
authors.lastname: Alizadeh
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
mesh_terms: D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009520:New Zealand; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D044465:White People
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22