The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples

Luis Rodríguez-Rodríguez; Wan Rohani Wan Taib; Ruth Topless; Sophia Steer; María F González-Escribano; Alejandro Balsa; Dora Pascual-Salcedo; Miguel A González-Gay; Enrique Raya; Benjamín Fernandez-Gutierrez; Isidoro González-Álvaro; Nunzio Bottini; Torsten Witte; Marte K Viken; Marieke J H Coenen; Piet L C M van Riel; Barbara Franke; Martin den Heijer; Timothy R D J Radstake; Paul Wordsworth; Benedicte A Lie; Tony R Merriman; Javier Martín

doi:10.1002/art.30145

The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples

Luis Rodríguez-Rodríguez, Wan Rohani Wan Taib, Ruth Topless, Sophia Steer, María F González-Escribano, Alejandro Balsa, Dora Pascual-Salcedo, Miguel A González-Gay, Enrique Raya, Benjamín Fernandez-Gutierrez, Isidoro González-Álvaro, Nunzio Bottini, Torsten Witte, Marte K Viken, Marieke J H Coenen, Piet L C M van Riel, Barbara Franke, Martin den Heijer, Timothy R D J Radstake, Paul WordsworthBenedicte A Lie, Tony R Merriman, Javier Martín

Research output: Contribution to journal › Article › Academic › peer-review

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]).

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.

Original language	English
Pages (from-to)	365-72
Number of pages	8
Journal	Arthritis and Rheumatism
Volume	63
Issue number	2
DOIs	https://doi.org/10.1002/art.30145
Publication status	Published - Feb 2011
Externally published	Yes

Keywords

Case-Control Studies
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Genotype
Humans
Male
Polymorphism, Single Nucleotide
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

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10.1002/art.30145

Cite this

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., ... Martín, J. (2011). The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples. Arthritis and Rheumatism, 63(2), 365-72. https://doi.org/10.1002/art.30145

@article{4193e98545f64434a63532453cea055c,

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]).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.",

keywords = "Case-Control Studies, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genotype, Humans, Male, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't",

author = "Luis Rodr{\'i}guez-Rodr{\'i}guez and Taib, {Wan Rohani Wan} and Ruth Topless and Sophia Steer and Gonz{\'a}lez-Escribano, {Mar{\'i}a F} and Alejandro Balsa and Dora Pascual-Salcedo and Gonz{\'a}lez-Gay, {Miguel A} and Enrique Raya and Benjam{\'i}n Fernandez-Gutierrez and Isidoro Gonz{\'a}lez-{\'A}lvaro and Nunzio Bottini and Torsten Witte and Viken, {Marte K} and Coenen, {Marieke J H} and {van Riel}, {Piet L C M} and Barbara Franke and {den Heijer}, Martin and Radstake, {Timothy R D J} and Paul Wordsworth and Lie, {Benedicte A} and Merriman, {Tony R} and Javier Mart{\'i}n",

note = "Copyright {\textcopyright} 2011 by the American College of Rheumatology.",

year = "2011",

month = feb,

doi = "10.1002/art.30145",

language = "English",

volume = "63",

pages = "365--72",

journal = "Arthritis and Rheumatism",

issn = "0004-3591",

publisher = "John Wiley & Sons Inc.",

number = "2",

}

Rodríguez-Rodríguez, L, Taib, WRW, Topless, R, Steer, S, González-Escribano, MF, Balsa, A, Pascual-Salcedo, D, González-Gay, MA, Raya, E, Fernandez-Gutierrez, B, González-Álvaro, I, Bottini, N, Witte, T, Viken, MK, Coenen, MJH, van Riel, PLCM, Franke, B, den Heijer, M, Radstake, TRDJ, Wordsworth, P, Lie, BA, Merriman, TR & Martín, J 2011, 'The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples', Arthritis and Rheumatism, vol. 63, no. 2, pp. 365-72. https://doi.org/10.1002/art.30145

TY - JOUR

T1 - The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples

AU - Rodríguez-Rodríguez, Luis

AU - Taib, Wan Rohani Wan

AU - Topless, Ruth

AU - Steer, Sophia

AU - González-Escribano, María F

AU - Balsa, Alejandro

AU - Pascual-Salcedo, Dora

AU - González-Gay, Miguel A

AU - Raya, Enrique

AU - Fernandez-Gutierrez, Benjamín

AU - González-Álvaro, Isidoro

AU - Bottini, Nunzio

AU - Witte, Torsten

AU - Viken, Marte K

AU - Coenen, Marieke J H

AU - van Riel, Piet L C M

AU - Franke, Barbara

AU - den Heijer, Martin

AU - Radstake, Timothy R D J

AU - Wordsworth, Paul

AU - Lie, Benedicte A

AU - Merriman, Tony R

AU - Martín, Javier

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

KW - Case-Control Studies

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 22

KW - Journal Article

KW - Multicenter Study

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/art.30145

DO - 10.1002/art.30145

M3 - Article

C2 - 21279993

SN - 0004-3591

VL - 63

SP - 365

EP - 372

JO - Arthritis and Rheumatism

JF - Arthritis and Rheumatism

IS - 2

ER -

The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples

Abstract

Keywords

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