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Genetic contribution of DKK-1 polymorphisms to RA structural severity and DKK-1 level of expression
  1. Corinne Miceli-Richard1,2,
  2. Kimberly E Taylor3,
  3. Joanne Nititham3,
  4. Raphaèle Seror1,
  5. Gaetane Nocturne2,
  6. Saida Boudaoud2,
  7. Philippe Dieude4,
  8. Arnaud Constantin5,
  9. Valérie Devauchelle-Pensec6,
  10. Gabriel J Tobón6,
  11. Xavier Mariette1,2,
  12. Lindsey A Criswell3
  1. 1 Service de Rhumatologie, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre, France
  2. 2 Unité INSERM U1012—Université Paris Sud, Le Kremlin Bicêtre, France
  3. 3 Division of rheumatology, Rosalind Russell / Ephraim P Engleman Rheumatology Research Center, University of California, San Francisco, California, USA
  4. 4 Service de rhumatologie, Assistance-Publique- Hôpitaux de Paris, Hôpital Bichat Claude-Bernard, Paris, France
  5. 5 INSERM, Toulouse III University and Department of Rheumatology, Purpan Hospital, CHU, Toulouse, France
  6. 6 CHU de la Cavale Blanche, Brest Cedex, France
  1. Correspondence to Corinne Miceli-Richard, Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, Le Kremlin Bicêtre 94275, France; corinne.miceli{at}bct.aphp.fr

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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 …

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