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Article Dans Une Revue Annals of the Rheumatic Diseases Année : 2014

Identification of Secreted Phosphoprotein 1 Gene as a new Rheumatoid Arthritis Susceptibility Gene

Gang Xie
  • Fonction : Auteur
Gilles Chioccia
  • Fonction : Auteur
Thomas Barnetche
Alain Cantagrel
  • Fonction : Auteur
  • PersonId : 1129425
Christophe Richez
Thierry Schaeverbeke
Robert Plenge
  • Fonction : Auteur

Résumé

Objective To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the RA genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. Methods We analyzed a total of 11,715 RA cases and 26,493 controls from 9 independent cohorts, all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on OPN expression in macrophages and OPN serum levels was investigated. Results We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥ 3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (P = 1.29x10-5, ORACPA-negative 1.257 1.135–1.394) and less with ACPA positivity (P = 0.0148, ORACPA-positive 1.072 1.014–1.134]). The odds ratios between these subgroups (i.e., ACPA-positive and -negative) significantly differed (P = 7.33x10-3). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (P = 0.0157) as well as serum level of secreted OPN correlated positively with ACPA production (P = 0.005; r = 0.483). Conclusion We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association greater in patients negative for ACPAs.

Domaines

Génétique

Dates et versions

inserm-01086600 , version 1 (24-11-2014)

Identifiants

Citer

Steven Gazal, Karim Sacre, Yannick Allanore, Maria Teruel, Alison H Goodall, et al.. Identification of Secreted Phosphoprotein 1 Gene as a new Rheumatoid Arthritis Susceptibility Gene. Annals of the Rheumatic Diseases, 2014, [Epub ahead of print]. ⟨10.1136/annrheumdis-2013-204581⟩. ⟨inserm-01086600⟩
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