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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; Cáliz, Rafael; Canet, Luz; Horst, Rob Ter; Bakker, Olivier; den Broeder, Alfons A; Martínez-Bueno, Manuel; Canhão, Helena; Rodríguez-Ramos, Ana; Lupiañez, Carmen B; Soto-Pino, María José; García, Antonio; Pérez-Pampin, Eva; González-Utrilla, Alfonso; Escudero, Alejandro; Segura-Catena, Juana; Netea-Maier, Romana T; Ferrer, Miguel Ángel; Collantes-Estevez, Eduardo; López Nevot, Miguel Ángel; Li, Yang; Jurado, Manuel; Fonseca, João E; Netea, Mihai G; Coenen, Marieke J H; Sainz, Juan.
Afiliação
  • Sánchez-Maldonado JM; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • Cáliz R; Instituto de Investigación Biosanataria IBs.Granada, Granada, Spain.
  • Canet L; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • Horst RT; Instituto de Investigación Biosanataria IBs.Granada, Granada, Spain.
  • Bakker O; Rheumatology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • den Broeder AA; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • Martínez-Bueno M; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
  • Canhão H; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Rodríguez-Ramos A; Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Lupiañez CB; Area of Genomic Medicine, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
  • Soto-Pino MJ; CEDOC, EpiDoC Unit, NOVA Medical School and National School of Public Health, Universidade Nova de Lisboa, Lisbon, Portugal.
  • García A; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • Pérez-Pampin E; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • González-Utrilla A; Rheumatology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • Escudero A; Rheumatology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • Segura-Catena J; Rheumatology Unit, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
  • Netea-Maier RT; Rheumatology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • Ferrer MÁ; Rheumatology department, Reina Sofía Hospital/IMIBIC/University of Córdoba, Córdoba, Spain.
  • Collantes-Estevez E; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • López Nevot MÁ; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
  • Li Y; Rheumatology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • Jurado M; Rheumatology department, Reina Sofía Hospital/IMIBIC/University of Córdoba, Córdoba, Spain.
  • Fonseca JE; Immunology department, Virgen de las Nieves University Hospital, Granada, Spain.
  • Netea MG; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Coenen MJH; Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Granada, Spain.
  • Sainz J; Instituto de Investigación Biosanataria IBs.Granada, Granada, Spain.
Sci Rep ; 9(1): 14812, 2019 10 15.
Article em En | MEDLINE | ID: mdl-31616008
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 IL1ß 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Hormônios Esteroides Gonadais / Doenças Ósseas / Citocromo P-450 CYP1B1 / Citocromo P-450 CYP2C9 Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Espanha País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Reumatoide / Hormônios Esteroides Gonadais / Doenças Ósseas / Citocromo P-450 CYP1B1 / Citocromo P-450 CYP2C9 Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Espanha País de publicação: Reino Unido