RT Journal Article
T1 Genetic Variants in RANK and OPG Could Influence Disease Severity and Bone Remodeling in Patients with Early Arthritis
A1 Triguero Martínez, Ana
A1 Pardines, Marisa
A1 Montes, Nuria
A1 Ortiz, Ana María
A1 De la Iglesia Cedeira, Alba
A1 Valero Martínez, Cristina
A1 Martín, Javier
A1 González Álvaro, Isidoro
A1 Castañeda, Santos
A1 Lamana Domínguez, Amalia
AB The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in bone remodeling-related genes associated with disease severity and bone mineral density (BMD) in early arthritis (EA) patients. For this purpose, the genotyping of 552 SNPs located in gene regions of semaphorins 4b, 4d, 4f, DKK1, 2 and 3, sclerostin, OPG, RANK and RANKL was performed using Immunochip from Illumina Inc. in 268 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study. Measurements of BMD and disease activity were chosen as outcome variables to select SNPs of interest. The relationships of SNPs with the BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) were analyzed by linear regression adjusted for age, sex, body mass index and presence of anti-citrullinated peptide antibodies (ACPAs). The association of each SNP with activity variables was analyzed by linear regression, logistic regression or ordered logistic regression according to the variable, and multivariate models were adjusted for potentially confounding variables, such as age, sex and presence of ACPAs. These analyses showed that four SNPs located in the genes coding for RANK (TNFRSF11A) and OPG (TNFRSF11B) were significantly associated with clinical variables of severity. SNP rs1805034 located in exon 6 of TNFRSF11A, which causes a non-synonymous (A/V) mutation, showed significant association with BMD and therefore may be considered as a possible biomarker of severity in RA patients. SNPs in the OPG gene showed an association with serum OPG levels and predicted disease activity after two years of follow-up.
PB MDPI
SN 2075-1729
YR 2024
FD 2024
LK https://hdl.handle.net/20.500.14352/111946
UL https://hdl.handle.net/20.500.14352/111946
LA eng
NO Triguero-Martínez, A., Pardines, M., Montes, N., Ortiz, A. M., de la Iglesia-Cedeira, A., Valero-Martínez, C., Martín, J., González-Álvaro, I., Castañeda, S., & Lamana, A. (2024). Genetic Variants in RANK and OPG Could Influence Disease Severity and Bone Remodeling in Patients with Early Arthritis. Life, 14(9). https://doi.org/10.3390/LIFE14091109
NO This research was funded by grant of the REI network (RD21/0002/0027) to A.T.-M., PI21/00526 to I.G-A. and PI21/01474 to S.C. from the Ministerio de Economía y Competitividad (INSTITUTO DE SALUD CARLOS III), co-funded by the European regional development fund (ERDF) “A way to make Europe”, and grant number RD21/0002/0004 to A.L., from “INSTITUTO DE SALUD CARLOS III”.  Finally, M.P. has an INVESTIGO grant from the Comunidad de Madrid. Genotyping was funded by project PI18/00371.
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO European Commission
NO Comunidad de Madrid
DS Docta Complutense
RD 17 abr 2025