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There is growing interest in the role of Dickkopf-1 (DKK-1), an inhibitor of the Wnt signalling pathway, in subchondral bone erosions in rheumatoid arthritis (RA). de Rooy et al 1 have previously reported that polymorphisms within the DKK-1 locus might contribute to RA structural severity. In fact, rs1896368 was significantly associated with an increased rate of joint destruction with a 1.02-fold (95% CI 1.01 to 1.04) progression rate per year per minor allele (additive model). Patients carrying the rs1896368 at-risk allele also had significantly higher serum levels of DKK-1. Several other polymorphisms located within the DKK-1 locus were associated with a faster structural progression.1 We aimed to replicate these findings in the ESPOIR cohort which is a prospective, multicentre French cohort of patients with early arthritis.2 We took advantage of the large number of patients assessed within the ESPOIR cohort, with iterative and centralised radiological evaluation, which allowed for studying the role of DKK-1 polymorphisms as predictive markers of structural damage and/or as genetic modulators of DKK-1 expression.3 Patients had to be free of disease-modifying antirheumatic drugs and biologics to be included in the cohort, thus avoiding a bias due …
Contributors CM-R and LAC: study conception and design. CM-R, GN, SB, PD, AC, VD-P, GJT and XM: acquisition of data. CMR, KT, JN, RSand LAC: data analysis. All authors were involved in drafting the manuscript or revising it critically for important intellectual content. All authors approved the final version to be published. CM-R had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses.
Funding An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the ESPOIR cohort study. Two additional grants from INSERM were obtained to support part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie and Roche-Chugai also supported the ESPOIR cohort study. A research grant from Pfizer ‘Passerelle’ was obtained for DKK-1 and SOST quantification for the whole cohort. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests None.
Patient consent Obtained.
Ethics approval French ethic committee board.
Provenance and peer review Not commissioned; externally peer reviewed.
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