FRI0014 GENETIC VARIABILITY IN MOLECULES REGULATING BONE REMODELING. DO THEY INFLUENCE SEVERITY OF DISEASE AND BONE MASS IN PATIENTS WITH EARLY-ONSET ARTHRITIS?
Authors: Noelia García Castañeda, Amalia Lamana, Nuria Montes, Ana Ortiz, Dolores Martinez-Quintanilla Jimenez, Cristina Valero, Pablo Moreno Fresneda, Irene Llorente, Javier Martin Ibanez, Carmen Martínez, Rosa P. Gomariz, Ana Triguero-Martinez, Santos Castañeda, Isidoro González-Álvaro
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> In the last few years, an association has been described between lower bone mass at the onset of disease and higher severity of rheumatoid arthritis (RA). <h3>Objectives:</h3> To identify single nucleotide polymorphisms (SNPs) in genes related to bone remodeling associated with severity of disease and bone mineral density (BMD) in patients with early-onset arthritis. <h3>Methods:</h3> We included 268 PEARL (Princess Early Arthritis Register Longitudinal) patients genotyped with Ilumina Inc. Immunochip. This array includes 556 SNPs with different density levels in semaphorins 4b, 4d and 4f, DKK1, 2 and 3, sclerostin, osteoprotegerin (OPG), RANK and RANKL. All SNPs with genotyping rate &lt;98%, with frequency of the minor allele &lt;1% and those that were not in Hardy-Weinberg equilibrium, were excluded. In addition, among the SNPs in linkage disequilibrium, a representative one was chosen, so that only 159 were finally studied. The intensity of treatment, the activity of the disease measured by the DAS28 and HUPI indices, as well as having achieved at least low activity after 2 years of follow-up were chosen as surrogate severity variables. The association of each of the SNPs with these variables was analyzed by linear regression, and ordered logistic regression according to the variable, and adjusted for potentially confusing variables, such as age, sex and presence of anti-cyclic citrullinated peptide antibodies. We selected those SNPs that were consistently associated with ≥3 surrogate severity variables, and then, the relationship of the selected SNPs with BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) was analyzed by means of linear regression adjusted for age and sex. <h3>Results:</h3> As shown in the attached table, 11 SNPs were associated with the severity of the disease; 7 of them were also associated with BMD, although only 3 confirmed the previously described relationship between severity of disease and BMD. <h3>Conclusion:</h3> This preliminary study highlights the relationship between gene variants of molecules involved in bone remodeling and the severity of early-onset arthritis. However, more studies are needed to confirm this relationship and validate it in other populations. This would confirm the involvement of these gene variants in disease activity and bone mass variation. <h3>References:</h3> [1] Llorente. I, et al. Anti-citrullinated protein antibodies are associated with decreased bone mineral density: baseline data from a register of early arthritis patients. Rheumatol Int. 2017;37(5):799-806 [2] Forslind K. et al. Hand bone loss measured by digital X-ray radiogrammetry is a predictor of joint damage in early rheumatoid arthritis. Scand J Rheumatol. 2009;38(6):431-8. <h3>Disclosure of Interests:</h3> Noelia García Castañeda: None declared, Amalia Lamana: None declared, Nuria Montes: None declared, Ana Ortiz: None declared, DOLORES MARTINEZ-QUINTANILLA JIMENEZ: None declared, Cristina Valero: None declared, PABLO MORENO FRESNEDA: None declared, Irene Llorente : None declared, Javier Martin Ibanez: None declared, Carmen Martínez: None declared, Rosa P. Gomariz: None declared, Ana Triguero-Martinez: None declared, Santos Castañeda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Isidoro González-Álvaro: None declared