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 Domínguez, Amalia
A1 Balsa, Alejandro
A1 Rueda, Blanca
A1 Ortiz, Ana
A1 Nuño, Laura
A1 Miranda-Carus, Maria Eugenia
A1 Gonzalez-Escribano, Maria
A1 Lopez-Nevot, Miguel
A1 Pascual-Salcedo, Dora
A1 Martin, Javier
A1 González-Álvaro, Isidoro
A2 Sawalha, Amr
AB Background. The 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 Results. We 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.Conclusions. Our 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 Libary of Science
SN 1932-6203
YR 2012
FD 2012
LK https://hdl.handle.net/20.500.14352/94457
UL https://hdl.handle.net/20.500.14352/94457
LA eng
NO Lamana A, Balsa A, Rueda B, Ortiz AM, Nuño L, Miranda-Carus ME, et al. (2012) The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis. PLoS ONE 7(8): e43661. https://doi.org/10.1371/journal.pone.0043661
NO This work was partially supported by the RETICS (Redes Tematicas de Investigación Cooperativa, Cooperative Research Thematic Networks) Program, RD08/0075 (RIER) and FIS (Fondo de Investigación en Salud) Health Research Fund grant FIS 08/0754 to IG-A from Instituto de Salud Carlos III (ISCIII; www.isciii.es) and by grants from the European Innovative Medicines Initiative and BTCure Program (http://www.life-sciences-europe.com/organisation/btcure-project-imiefpia-201103-innovative-medicines-initiative-2001-28657.html). The work of IG-A was in part supported by a Research Intensification Grant from the National Health Care System (Instituto Carlos III; www.isciii.es), Madrid, Spain.
NO Instituto de Salud Carlos III
DS Docta Complutense
RD 7 abr 2025