Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region

Jose-Ezequiel Martín; Behrooz Z Alizadeh; Miguel A González-Gay; Alejandro Balsa; Dora Pascual-Salcedo; María F González-Escribano; Luis Rodriguez-Rodriguez; Benjamín Fernández-Gutiérrez; Enrique Raya; Marieke J H Coenen; Piet van Riel; Timothy R D J Radstake; Tore K Kvien; Marte K Viken; Benedicte A Lie; Bobby P C Koeleman; Javier Martín

doi:10.3899/jrheum.110361

Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region

Jose-Ezequiel Martín, Behrooz Z Alizadeh, Miguel A González-Gay, Alejandro Balsa, Dora Pascual-Salcedo, María F González-Escribano, Luis Rodriguez-Rodriguez, Benjamín Fernández-Gutiérrez, Enrique Raya, Marieke J H Coenen, Piet van Riel, Timothy R D J Radstake, Tore K Kvien, Marte K Viken, Benedicte A Lie, Bobby P C Koeleman, Javier Martín

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

Abstract

OBJECTIVE: The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.

METHODS: We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10(-3)) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway.

RESULTS: We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601.

CONCLUSION: The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA.

Original language	English
Pages (from-to)	2290-6
Number of pages	7
Journal	Journal of Rheumatology
Volume	38
Issue number	11
DOIs	https://doi.org/10.3899/jrheum.110361
Publication status	Published - Nov 2011

Keywords

Arthritis, Rheumatoid
Case-Control Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Netherlands
Norway
Polymorphism, Single Nucleotide
Protein Tyrosine Phosphatase, Non-Receptor Type 22
Risk Factors
Spain
Journal Article
Research Support, Non-U.S. Gov't

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10.3899/jrheum.110361

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Martín, J.-E., Alizadeh, B. Z., González-Gay, M. A., Balsa, A., Pascual-Salcedo, D., González-Escribano, M. F., Rodriguez-Rodriguez, L., Fernández-Gutiérrez, B., Raya, E., Coenen, M. J. H., van Riel, P., Radstake, T. R. D. J., Kvien, T. K., Viken, M. K., Lie, B. A., Koeleman, B. P. C., & Martín, J. (2011). Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region. Journal of Rheumatology, 38(11), 2290-6. https://doi.org/10.3899/jrheum.110361

@article{1aefaac74df34c87af1ca59fb1696e4e,

title = "Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region",

abstract = "OBJECTIVE: The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.METHODS: We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10(-3)) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway.RESULTS: We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601.CONCLUSION: The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA.",

keywords = "Arthritis, Rheumatoid, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Netherlands, Norway, Polymorphism, Single Nucleotide, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Risk Factors, Spain, Journal Article, Research Support, Non-U.S. Gov't",

author = "Jose-Ezequiel Mart{\'i}n and Alizadeh, \{Behrooz Z\} and Gonz{\'a}lez-Gay, \{Miguel A\} and Alejandro Balsa and Dora Pascual-Salcedo and Gonz{\'a}lez-Escribano, \{Mar{\'i}a F\} and Luis Rodriguez-Rodriguez and Benjam{\'i}n Fern{\'a}ndez-Guti{\'e}rrez and Enrique Raya and Coenen, \{Marieke J H\} and \{van Riel\}, Piet and Radstake, \{Timothy R D J\} and Kvien, \{Tore K\} and Viken, \{Marte K\} and Lie, \{Benedicte A\} and Koeleman, \{Bobby P C\} and Javier Mart{\'i}n",

year = "2011",

month = nov,

doi = "10.3899/jrheum.110361",

language = "English",

volume = "38",

pages = "2290--6",

journal = "Journal of Rheumatology",

issn = "0315-162X",

publisher = "Journal of Rheumatology",

number = "11",

}

Martín, J-E, Alizadeh, BZ, González-Gay, MA, Balsa, A, Pascual-Salcedo, D, González-Escribano, MF, Rodriguez-Rodriguez, L, Fernández-Gutiérrez, B, Raya, E, Coenen, MJH, van Riel, P, Radstake, TRDJ, Kvien, TK, Viken, MK, Lie, BA, Koeleman, BPC & Martín, J 2011, 'Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region', Journal of Rheumatology, vol. 38, no. 11, pp. 2290-6. https://doi.org/10.3899/jrheum.110361

TY - JOUR

T1 - Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region

AU - Martín, Jose-Ezequiel

AU - Alizadeh, Behrooz Z

AU - González-Gay, Miguel A

AU - Balsa, Alejandro

AU - Pascual-Salcedo, Dora

AU - González-Escribano, María F

AU - Rodriguez-Rodriguez, Luis

AU - Fernández-Gutiérrez, Benjamín

AU - Raya, Enrique

AU - Coenen, Marieke J H

AU - van Riel, Piet

AU - Radstake, Timothy R D J

AU - Kvien, Tore K

AU - Viken, Marte K

AU - Lie, Benedicte A

AU - Koeleman, Bobby P C

AU - Martín, Javier

PY - 2011/11

Y1 - 2011/11

N2 - OBJECTIVE: The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.METHODS: We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10(-3)) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway.RESULTS: We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601.CONCLUSION: The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA.

AB - OBJECTIVE: The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.METHODS: We analyzed Wellcome Trust Case-Control Consortium genome-wide association study data for associations in the 397.2 kb PTPN22 region and selected 9 associated SNP (with p < 5 × 10(-3)) for replication and dependence analysis. The replication cohorts comprised 2857 patients with RA and 2994 controls from Spain, Netherlands, and Norway.RESULTS: We found that 6 of the 9 selected SNP were associated in the Spanish cohort. Of these, 4 were also associated in the Dutch and Norwegian cohorts, and all 6 were associated with RA in the combined analysis. Conditional analyses showed that none of these associations was independent of rs2476601.CONCLUSION: The SNP rs2476601 located in the PTPN22 gene is the sole common genetic variant associated with RA in the 1p13.2 region, suggesting that neighbor genes of PTPN22 do not have a major influence in RA.

KW - Arthritis, Rheumatoid

KW - Case-Control Studies

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Netherlands

KW - Norway

KW - Polymorphism, Single Nucleotide

KW - Protein Tyrosine Phosphatase, Non-Receptor Type 22

KW - Risk Factors

KW - Spain

KW - Journal Article

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

U2 - 10.3899/jrheum.110361

DO - 10.3899/jrheum.110361

M3 - Article

C2 - 21965649

SN - 0315-162X

VL - 38

SP - 2290

EP - 2296

JO - Journal of Rheumatology

JF - Journal of Rheumatology

IS - 11

ER -

Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region

Abstract

Keywords

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