The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis
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AutorLamana, Amalia; Balsa, Alejandro; Rueda Medina, Blanca; Ortiz, Ana M.; Nuño, Laura; Miranda-Carus, María Eugenia; González-Escribano, María F.; López Nevot, Miguel Ángel; Pascual Salcedo, Dora; Martín Ibáñez, Javier; González-Álvaro, Isidoro
Public Library of Science (PLOS)
AllelesArthritisDisabilitiesGenetics of diseaseGenetics of the immune systemHuman geneticsRheumatoid arthritisVariant genotypes
Lamana, A.; 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, 7(8): e43661 (2012). [http://hdl.handle.net/10481/31147]
PatrocinadorThis 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-imi-efpia-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.
[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.