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

Autor: Alfonso González-Utrilla, Alfons A den Broeder, Rafael Cáliz, Juan Sainz, Jose Manuel Sánchez-Maldonado, Romana T. Netea-Maier, Eduardo Collantes-Estevez, Rob ter Horst, María José Soto-Pino, Ana Rodríguez-Ramos, Miguel Ferrer, Yang Li, Marieke J H Coenen, Manuel Martínez-Bueno, Eva Perez-Pampin, Olivier B. Bakker, L. M. Canet, Manuel Jurado, Alejandro Escudero, Mihai G. Netea, João Eurico Fonseca, Juana Segura-Catena, Carmen Belén Lupiañez, Miguel Ángel López Nevot, Helena Canhão, Antonio García
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
lcsh:Medicine
Arthritis
Gastroenterology
Arthritis
Rheumatoid
Prognostic markers
0302 clinical medicine
Sex hormone-binding globulin
SYSTEMIC-LUPUS-ERYTHEMATOSUS
Gonadal Steroid Hormones
lcsh:Science
VITAMIN-D
education.field_of_study
IGG FC-RECEPTOR
Multidisciplinary
biology
Middle Aged
Prognosis
Rheumatoid arthritis
Cytochrome P-450 CYP1B1
Disease Progression
Female
Bone Diseases
ESTROGEN-RECEPTOR-ALPHA
Adult
medicine.medical_specialty
Population
Single-nucleotide polymorphism
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Polymorphism
Single Nucleotide
GENE POLYMORPHISMS
Article
03 medical and health sciences
REPLACEMENT THERAPY
All institutes and research themes of the Radboud University Medical Center
SYNOVIAL-FLUID
Predictive Value of Tests
Rheumatoid Factor
Internal medicine
medicine
Vitamin D and neurology
Humans
Rheumatoid factor
education
Aged
Cytochrome P-450 CYP2C9
Retrospective Studies
030203 arthritis & rheumatology
business.industry
lcsh:R
NECROSIS-FACTOR-ALPHA
medicine.disease
Steroid hormone
030104 developmental biology
Haplotypes
Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5]
biology.protein
IMMUNE-COMPLEXES
lcsh:Q
MINERAL DENSITY
business
Zdroj: Scientific Reports, 9:14812. Nature Publishing Group
Scientific Reports, 9
Scientific Reports, Vol 9, Iss 1, Pp 1-16 (2019)
Digibug. Repositorio Institucional de la Universidad de Granada
instname
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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