Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis
Por:
Diaz-Gallo, L, 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, Garcia-Hernandez, FJ, Carreira, P, Camps, MT, Fernandez-Nebro, A, de la Pena, PG, Nearney, T, Hilda, D, Gonzalez-Gay, MA, Airo, P, Beretta, L, Scorza, R, Herrick, A, Worthington, J, Pros, A, Gomez-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
Publicada:
1 mar 2011
Resumen:
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.
Filiaciones:
Diaz-Gallo, L:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain
Gourh, P:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Broen, J:
Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands
Simeon, C:
Hosp Valle De Hebron, Med Interna Serv, Barcelona, Spain
Fonollosa, V:
Hosp Valle De Hebron, Med Interna Serv, Barcelona, Spain
Ortego-Centeno, N:
Hosp Clin Univ, Med Interna Serv, Granada, Spain
Agarwal, S:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Vonk, MC:
Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands
Coenen, M:
Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands
Riemekasten, G:
Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany
Hunzelmann, N:
Univ Cologne, Dept Dermatol, D-5000 Cologne 41, Germany
Hesselstrand, R:
Univ Lund Hosp, Dept Rheumatol, S-22185 Lund, Sweden
Tan, FK:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Reveille, JD:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Assassi, S:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Garcia-Hernandez, FJ:
Hosp Virgen Rocio, Med Interna Serv, Seville, Spain
Carreira, P:
Hosp 12 Octubre, Serv Reumatol, E-28041 Madrid, Spain
Camps, MT:
Hosp Carlos Haya, Med Interna Serv, Malaga, Spain
Fernandez-Nebro, A:
Hosp Carlos Haya, Serv Reumatol, Malaga, Spain
de la Pena, PG:
Hosp Ramon & Cajal, Serv Reumatol, E-28034 Madrid, Spain
Nearney, T:
Univ Texas Med Branch Galveston, Galveston, TX USA
Hilda, D:
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA
Gonzalez-Gay, MA:
Hosp Marques de Valdecilla, Serv Reumatol, Santander, Spain
Airo, P:
Clin Spedali Civili, Serv Reumatol & Immunol, Brescia, Italy
Beretta, L:
Univ Milan, Referral Ctr Syst Autoimmune Dis, Milan, Italy
Scorza, R:
Univ Milan, Referral Ctr Syst Autoimmune Dis, Milan, Italy
Herrick, A:
Univ Manchester, Ctr Rheumat Dis, Salford Royal NHS Fdn Trust, Manchester M13 9PL, Lancs, England
Worthington, J:
Univ Manchester, Ctr Rheumat Dis, Salford Royal NHS Fdn Trust, Manchester M13 9PL, Lancs, England
Pros, A:
Hosp del Mar, Serv Reumatol, Barcelona, Spain
Gomez-Gracia, I:
Hosp Reina Sofia, Serv Reumatol, Cordoba, Spain
Trapiella, L:
Hosp Univ Cent Asturias, Med Interna Serv, Oviedo, Spain
Espinosa, G:
Hosp Clin Barcelona, Med Interna Serv, Barcelona, Spain
Castellvi, I:
Hosp Santa Creu & Sant Pau, Serv Reumatol, Barcelona, Spain
Witte, T:
Hannover Med Sch, D-3000 Hannover, Germany
de Keyser, F:
Univ Ghent, Dept Rheumatol, Ghent, Belgium
Vanthuyne, M:
Catholic Univ Louvain, Dept Rheumatol, B-3000 Louvain, Belgium
Mayes, MD:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Radstake, TRDJ:
Radboud Univ Nijmegen, Med Ctr, Dept Rheumatol, NL-6525 ED Nijmegen, Netherlands
Arnett, FC:
Univ Texas Hlth Sci Ctr Houston Med Sch, Dept Internal Med, Div Rheumatol & Clin Immunogenet, Houston, TX USA
Martin, J:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain
Rueda, B:
CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain
Green Accepted
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