Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

L. M. Diaz-Gallo; P. Gourh; J. Broen; C. Simeon; V. Fonollosa; N. Ortego-Centeno; S. Agarwal; M. C. Vonk; M. Coenen; G. Riemekasten; N. Hunzelmann; R. Hesselstrand; F. K. Tan; J. D. Reveille; S. Assassi; F. J. García-Hernandez; P. Carreira; M. T. Camps; A. Fernandez-Nebro; P. Garcia De La Peña; T. Nearney; D. Hilda; M. A. González-Gay; P. Airo; L. Beretta; R. Scorza; A. Herrick; J. Worthington; A. Pros; I. Gómez-Gracia; L. Trapiella; G. Espinosa; I. Castellvi; T. Witte; F. De Keyser; M. Vanthuyne; M. D. Mayes; T. R D J Radstake; F. C. Arnett; J. Martin; Blanca Rueda

doi:10.1136/ard.2010.130138

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

L. M. Diaz-Gallo, P. Gourh, J. Broen, C. Simeon, V. Fonollosa, N. Ortego-Centeno, S. Agarwal, M. C. Vonk, M. Coenen, G. Riemekasten, N. Hunzelmann, R. Hesselstrand, F. K. Tan, J. D. Reveille, S. Assassi, F. J. García-Hernandez, P. Carreira, M. T. Camps, A. Fernandez-Nebro, P. Garcia De La PeñaT. Nearney, D. Hilda, M. A. González-Gay, P. Airo, L. Beretta, R. Scorza, A. Herrick, J. Worthington, A. Pros, I. Gómez-Gracia, L. Trapiella, G. Espinosa, I. Castellvi, T. Witte, F. De Keyser, M. Vanthuyne, M. D. Mayes, T. R D J Radstake, F. C. Arnett, J. Martin, Blanca Rueda

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

Abstract

Objective: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case - control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p FDRcorrected =0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p FDRcorrected =0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p FDRcorrected =0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

Original language	English
Pages (from-to)	454-462
Number of pages	8
Journal	Annals of the rheumatic diseases
Volume	70
Issue number	3
DOIs	https://doi.org/10.1136/ard.2010.130138
Publication status	Published - Mar 2011

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Diaz-Gallo, L. M., Gourh, P., Broen, J., Simeon, C., Fonollosa, V., Ortego-Centeno, N., Agarwal, S., Vonk, M. C., Coenen, M., Riemekasten, G., Hunzelmann, N., Hesselstrand, R., Tan, F. K., Reveille, J. D., Assassi, S., García-Hernandez, F. J., Carreira, P., Camps, M. T., Fernandez-Nebro, A., ... Rueda, B. (2011). Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis. Annals of the rheumatic diseases, 70(3), 454-462. https://doi.org/10.1136/ard.2010.130138

@article{5ab2d540ea484f7897d0a418d8475864,

title = "Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis",

abstract = "Objective: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case - control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p FDRcorrected =0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p FDRcorrected =0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p FDRcorrected =0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.",

author = "Diaz-Gallo, {L. M.} and P. Gourh and J. Broen and C. Simeon and V. Fonollosa and N. Ortego-Centeno and S. Agarwal and Vonk, {M. C.} and M. Coenen and G. Riemekasten and N. Hunzelmann and R. Hesselstrand and Tan, {F. K.} and Reveille, {J. D.} and S. Assassi and Garc{\'i}a-Hernandez, {F. J.} and P. Carreira and Camps, {M. T.} and A. Fernandez-Nebro and {Garcia De La Pe{\~n}a}, P. and T. Nearney and D. Hilda and Gonz{\'a}lez-Gay, {M. A.} and P. Airo and L. Beretta and R. Scorza and A. Herrick and J. Worthington and A. Pros and I. G{\'o}mez-Gracia and L. Trapiella and G. Espinosa and I. Castellvi and T. Witte and {De Keyser}, F. and M. Vanthuyne and Mayes, {M. D.} and Radstake, {T. R D J} and Arnett, {F. C.} and J. Martin and Blanca Rueda",

note = "2010 Dec 3. [Epub ahead of print]",

year = "2011",

month = mar,

doi = "10.1136/ard.2010.130138",

language = "English",

volume = "70",

pages = "454--462",

journal = "Annals of the rheumatic diseases",

issn = "0003-4967",

publisher = "BMJ ",

number = "3",

}

Diaz-Gallo, LM, Gourh, P, Broen, J, Simeon, C, Fonollosa, V, Ortego-Centeno, N, Agarwal, S, Vonk, MC, Coenen, M, Riemekasten, G, Hunzelmann, N, Hesselstrand, R, Tan, FK, Reveille, JD, Assassi, S, García-Hernandez, FJ, Carreira, P, Camps, MT, Fernandez-Nebro, A, Garcia De La Peña, P, Nearney, T, Hilda, D, González-Gay, MA, Airo, P, Beretta, L, Scorza, R, Herrick, A , Worthington, J, Pros, A, Gómez-Gracia, I, Trapiella, L, Espinosa, G, Castellvi, I, Witte, T, De Keyser, F, Vanthuyne, M, Mayes, MD, Radstake, TRDJ, Arnett, FC, Martin, J & Rueda, B 2011, 'Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis', Annals of the rheumatic diseases, vol. 70, no. 3, pp. 454-462. https://doi.org/10.1136/ard.2010.130138

TY - JOUR

T1 - Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

AU - Diaz-Gallo, L. M.

AU - Gourh, P.

AU - Broen, J.

AU - Simeon, C.

AU - Fonollosa, V.

AU - Ortego-Centeno, N.

AU - Agarwal, S.

AU - Vonk, M. C.

AU - Coenen, M.

AU - Riemekasten, G.

AU - Hunzelmann, N.

AU - Hesselstrand, R.

AU - Tan, F. K.

AU - Reveille, J. D.

AU - Assassi, S.

AU - García-Hernandez, F. J.

AU - Carreira, P.

AU - Camps, M. T.

AU - Fernandez-Nebro, A.

AU - Garcia De La Peña, P.

AU - Nearney, T.

AU - Hilda, D.

AU - González-Gay, M. A.

AU - Airo, P.

AU - Beretta, L.

AU - Scorza, R.

AU - Herrick, A.

AU - Worthington, J.

AU - Pros, A.

AU - Gómez-Gracia, I.

AU - Trapiella, L.

AU - Espinosa, G.

AU - Castellvi, I.

AU - Witte, T.

AU - De Keyser, F.

AU - Vanthuyne, M.

AU - Mayes, M. D.

AU - Radstake, T. R D J

AU - Arnett, F. C.

AU - Martin, J.

AU - Rueda, Blanca

N1 - 2010 Dec 3. [Epub ahead of print]

PY - 2011/3

Y1 - 2011/3

N2 - Objective: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case - control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p FDRcorrected =0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p FDRcorrected =0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p FDRcorrected =0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

AB - Objective: Two functional single nucleotide polymorphisms (SNP) in the PTPN22 gene (rs24746601 and rs33996649) have been associated with autoimmunity. The aim of this study was to investigate the role of the R263Q SNP for the first time and to re-evaluate the role of the R620W SNP in the genetic predisposition to systemic sclerosis (SSc) susceptibility and clinical phenotypes. Methods: 3422 SSc patients (2020 with limited cutaneous SSc and 1208 with diffuse cutaneous SSc) and 3638 healthy controls of Caucasian ancestry from an initial case - control set of Spain and seven additional independent replication cohorts were included in our study. Both rs33996649 and rs2476601 PTPN22 polymorphisms were genotyped by TaqMan allelic discrimination assay. A meta-analysis was performed to test the overall effect of these PTPN22 polymorphisms in SSc. Results: The meta-analysis revealed evidence of association of the rs2476601 T allele with SSc susceptibility (p FDRcorrected =0.03 pooled, OR 1.15, 95% CI 1.03 to 1.28). In addition, the rs2476601 T allele was significantly associated with anticentromere-positive status (p FDRcorrected =0.02 pooled, OR 1.22, 95% CI 1.05 to 1.42). Although the rs33996649 A allele was significantly associated with SSc in the Spanish population (p FDRcorrected =0.04, OR 0.58, 95% CI 0.36 to 0.92), this association was not confirmed in the meta-analysis (p=0.36 pooled, OR 0.89, 95% CI 0.72 to 1.1). Conclusion: The study suggests that the PTPN22 R620W polymorphism influences SSc genetic susceptibility but the novel R263Q genetic variant does not. These data strengthen evidence that the R620W mutation is a common risk factor in autoimmune diseases.

U2 - 10.1136/ard.2010.130138

DO - 10.1136/ard.2010.130138

M3 - Article

C2 - 21131644

SN - 0003-4967

VL - 70

SP - 454

EP - 462

JO - Annals of the rheumatic diseases

JF - Annals of the rheumatic diseases

IS - 3

ER -

Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis

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