RT Journal Article
T1 The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis
A1 Lamana, Amalia
A1 Balsa, Alejandro
A1 Rueda, Blanca
A1 Ortiz, Ana M
A1 Nuño, Laura
A1 Miranda-Carus, Maria Eugenia
A1 Gonzalez-Escribano, Maria F
A1 Lopez-Nevot, Miguel A
A1 Pascual-Salcedo, Dora
A1 Martin, Javier
A1 González-Álvaro, Isidoro
K1 STAT4 Transcription Factor
K1 PTPN22 protein, human
K1 Protein Tyrosine Phosphatase, Non-Receptor Type 22
K1 HLA-DRB1 Chains
K1 Anciano
K1 Alelos
K1 Artritis
K1 Evaluación de la Discapacidad
K1 Predisposición Genética a la Enfermedad
K1 Genotipo
K1 Mediana Edad
K1 Polimorfismo de Nucleótido Simple
K1 Factor de Transcripción STAT4
K1 Índice de Severidad de la Enfermedad
K1 Adulto
AB BACKGROUNDThe number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.METHODOLOGY AND RESULTSWe studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.CONCLUSIONSOur data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.
PB Public Library of Science
YR 2012
FD 2012-08-24
LK http://hdl.handle.net/10668/1408
UL http://hdl.handle.net/10668/1408
LA en
NO Lamana A, Balsa A, Rueda B, Ortiz AM, Nuño L, Miranda-Carus ME, et al. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis. PLoS ONE. 2012; 7(8):e43661
NO Journal Article; Research Support, Non-U.S. Gov't.                                      The authors have read the journal’s policy and some authors have the following conflicts: Unrestricted research grants have been provided by Roche, UCB and Bristol-Myers Squibb to IG-A; and by Abbott Laboratories and Roche to LN. All these research projects have no relation with the present study. AB holds an advisory board membership with Pfizer and UCB. The following authors hold Honoraria for speaking: IG-A (Spanish Society of Rheumatology (SER), Rheumatology Society of Madrid (SORCOM), Roche, Abbott Laboratories and Bristol-Myers Squibb); AB (Roche, Schering-Plough, Wyeth, Abbott, BMS, Janssen and UCB); AMO (Spanish Society of Rheumatology (SER), Laboratorios Esteve, Abbott Laboratories and MSD); JM (Spanish Society of Rheumatology (SER)); and LN (Abbott Laboratories). The remaining authors have declared that no competing interests exist. There are no patents, products indevelopment or marketed products to declare. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials, as detailed online on the guide for authors.
DS RISalud
RD Apr 7, 2025