RT Journal Article
T1 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.
A1 Sanchez-Maldonado, Jose M
A1 Caliz, Rafael
A1 Canet, Luz
A1 Horst, Rob Ter
A1 Bakker, Olivier
A1 den Broeder, Alfons A
A1 Martinez-Bueno, Manuel
A1 Canhão, Helena
A1 Rodriguez-Ramos, Ana
A1 Lupiañez, Carmen B
A1 Soto-Pino, Maria Jose
A1 Garcia, Antonio
A1 Perez-Pampin, Eva
A1 Gonzalez-Utrilla, Alfonso
A1 Escudero, Alejandro
A1 Segura-Catena, Juana
A1 Netea-Maier, Romana T
A1 Ferrer, Miguel Angel
A1 Collantes-Estevez, Eduardo
A1 Lopez Nevot, Miguel Angel
A1 Li, Yang
A1 Jurado, Manuel
A1 Fonseca, João E
A1 Netea, Mihai G
A1 Coenen, Marieke J H
A1 Sainz, Juan
K1 Polymorphism, single nucleotide
K1 Predictive value of tests
K1 Prognosis
K1 Retrospective studies
K1 Rheumatoid factor
AB 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.
PB Nature Publishing Group
YR 2019
FD 2019-09-28
LK http://hdl.handle.net/10668/14834
UL http://hdl.handle.net/10668/14834
LA en
NO Sánchez-Maldonado JM, Cáliz R, Canet L, Horst RT, Bakker O, den Broeder AA, et al. 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. Sci Rep. 2019 Oct 15;9(1):14812
NO Tis study was supported by a research grant from FIBAO foundation.
DS RISalud
RD Apr 6, 2025