title: The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples.
abstract: OBJECTIVE
  Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA).
  
  
  METHODS
  RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5'-allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined.
  
  
  RESULTS
  The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel-Haenszel pooled OR 0.80 [95% CI 0.67-0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05-1.55], for 3 versus 1 risk allele P = 6.67 × 10(-11) , OR 2.01 [1.63-2.48], and for 4 versus 1 risk allele P = 6.50 × 10(-11) , OR 3.55 [2.42-5.20]).
  
  
  CONCLUSIONS
  Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well-established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.
authors.affiliation: Instituto de Parasitología y Biomedicina Lopez-Neyra, CSIC, Armilla and Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Rodríguez-Rodríguez
authors.forename: Wan Rohani Wan
authors.initials: WR
authors.lastname: Taib
authors.forename: Ruth
authors.initials: R
authors.lastname: Topless
authors.forename: Sophia
authors.initials: S
authors.lastname: Steer
authors.forename: María F
authors.initials: MF
authors.lastname: González-Escribano
authors.forename: Alejandro
authors.initials: A
authors.lastname: Balsa
authors.forename: Dora
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: Miguel A
authors.initials: MA
authors.lastname: González-Gay
authors.forename: Enrique
authors.initials: E
authors.lastname: Raya
authors.forename: Benjamín
authors.initials: B
authors.lastname: Fernandez-Gutierrez
authors.forename: Isidoro
authors.initials: I
authors.lastname: González-Álvaro
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Marte K
authors.initials: MK
authors.lastname: Viken
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
authors.forename: Javier
authors.initials: J
authors.lastname: Martín
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22