Open AccessThe PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case–control samples
Author(s) -
RodríguezRodríguez Luis,
Taib Wan Rohani Wan,
Topless Ruth,
Steer Sophia,
GonzálezEscribano María F.,
Balsa Alejandro,
PascualSalcedo Dora,
GonzálezGay Miguel A.,
Raya Enrique,
FernandezGutierrez Benjamín,
GonzálezÁlvaro Isidoro,
Bottini Nunzio,
Witte Torsten,
Viken Marte K.,
Coenen Marieke J. H.,
van Riel Piet L. C. M.,
Franke Barbara,
den Heijer Martin,
Radstake Timothy R. D. J.,
Wordsworth Paul,
Lie Benedicte A.,
Merriman Tony R.,
Martín Javier
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30145
Subject(s) - ptpn22 , odds ratio , rheumatoid arthritis , allele , medicine , confidence interval , gastroenterology , genotype , immunology , biology , genetics , single nucleotide polymorphism , gene
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]). Conclusion 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.