@misc{10481/57679,
year = {2019},
month = {10},
url = {http://hdl.handle.net/10481/57679},
abstract = {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.},
publisher = {Springer Nature},
title = {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},
doi = {10.1038/s41598-019-51255-0},
author = {Sánchez Maldonado, José and Cáliz Cáliz, Antonio Rafael and Canet Antequera, Luz María and Martínez Bueno, Manuel and Rodríguez Ramos, Ana and Lupiañez, Carmen and Soto Pino, María José and Garcia, Antonio and González Utrilla, Alfonso and Segura Catena, Juana and Jurado Chacón, Manuel and López Nevot, Miguel Ángel},
}