Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium
Metadatos
Mostrar el registro completo del ítemAutor
Sánchez Maldonado, José; Cáliz Cáliz, Antonio Rafael; Canet Antequera, Luz María; Martínez Bueno, Manuel; Rodríguez Ramos, Ana; Lupiañez, Carmen; Soto Pino, María José; Garcia, Antonio; González Utrilla, Alfonso; Segura Catena, Juana; Jurado Chacón, Manuel; López Nevot, Miguel ÁngelEditorial
Springer Nature
Fecha
2019-10-15Referencia bibliográfica
Sánchez-Maldonado, J. M., Cáliz, R., Canet, L., ter Horst, R., Bakker, O., den Broeder, A. A., ... & Soto-Pino, M. J. (2019). Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium. Scientific Reports, 9(1), 1-16.
Resumen
Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease.
The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2,
FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and
0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry
(P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a
gender-specific correlation of the CYP2C9rs1799853T/T genotype with serum vitamin D3 levels (P = 0.00085)
and a modest effect on IL1β levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057
and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with
a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed
that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or
macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10−7). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease
in seropositive patients (PRF+ = 2.46•10−8) whereas no prediction was detected in seronegative patients
(PRF− = 0.36). Although the predictive ability of the model was substantially lower in the replication
population (PRF+ = 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive
disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid
hormone-related polymorphisms with erosive disease.