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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.


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, Fc?R3A, 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 IL1? 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 Fc?R3A 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.

SUBMITTER: Sanchez-Maldonado JM 

PROVIDER: S-EPMC6794376 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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.

Sánchez-Maldonado Jose M JM   Cáliz Rafael R   Canet Luz L   Horst Rob Ter RT   Bakker Olivier O   den Broeder Alfons A AA   Martínez-Bueno Manuel M   Canhão Helena H   Rodríguez-Ramos Ana A   Lupiañez Carmen B CB   Soto-Pino María José MJ   García Antonio A   Pérez-Pampin Eva E   González-Utrilla Alfonso A   Escudero Alejandro A   Segura-Catena Juana J   Netea-Maier Romana T RT   Ferrer Miguel Ángel MÁ   Collantes-Estevez Eduardo E   López Nevot Miguel Ángel MÁ   Li Yang Y   Jurado Manuel M   Fonseca João E JE   Netea Mihai G MG   Coenen Marieke J H MJH   Sainz Juan J  

Scientific reports 20191015 1


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-spe  ...[more]

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