Dr. González-Álvaro has received consulting fees, speaking fees, and/or honoraria from Abbott and Roche (less than $10,000 each).
The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case–control samples
Article first published online: 28 JAN 2011
Copyright © 2011 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 63, Issue 2, pages 365–372, February 2011
How to Cite
Rodríguez-Rodríguez, L., Taib, W. R. W., Topless, R., Steer, S., González-Escribano, M. F., Balsa, A., Pascual-Salcedo, D., González-Gay, M. A., Raya, E., Fernandez-Gutierrez, B., González-Álvaro, I., Bottini, N., Witte, T., Viken, M. K., Coenen, M. J. H., van Riel, P. L. C. M., Franke, B., den Heijer, M., Radstake, T. R. D. J., Wordsworth, P., Lie, B. A., Merriman, T. R. and Martín, J. (2011), The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case–control samples. Arthritis & Rheumatism, 63: 365–372. doi: 10.1002/art.30145
- Issue published online: 28 JAN 2011
- Article first published online: 28 JAN 2011
- Accepted manuscript online: 15 NOV 2010 12:00PM EST
- Manuscript Accepted: 4 NOV 2010
- Manuscript Received: 13 JUL 2010
- Junta de Andalucía (Group CTS-180)
- Instituto de Salud Carlos III (RETICS Program RD08/0075–RIER)
- Fundacion Mutua Madrileña. Grant Number: PI-668
- Health Research Council of New Zealand, Arthritis New Zealand
- Medical Research Council (UK)
- University of Oxford (Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences departmental grant)
- South and Eastern Norway Regional Health Authority
- Fondo de Investigaciones Sanitarias contract (CM08/00218, Spain)
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).
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.
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]).
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.