title: Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts).
abstract: OBJECTIVE
  To assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.
  
  
  METHODS
  This work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.
  
  
  RESULTS
  The AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14-3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68-6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94-18.69], p = 0.002) on the risk of erosions in ACPA+ patients.
  
  
  CONCLUSIONS
  A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.
authors.affiliation: INSERM, UMR1027, 31062 Toulouse cedex 9, France; Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France; Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France. Electronic address: adruyssen@hotmail.com.
authors.forename: Adeline
authors.initials: A
authors.lastname: Ruyssen-Witrand
authors.affiliation: Rheumatology Department, Lapeyronie Teaching Hospital, 34295 Montpellier cedex 5, France.
authors.forename: Cedric
authors.initials: C
authors.lastname: Lukas
authors.affiliation: Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Nigon
authors.affiliation: Rheumatology Department, Claude Bernard-Bichat Teaching Hospital, Paris VII University, 75890 Paris cedex 18, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Dawidowicz
authors.affiliation: Rheumatology Department, Lapeyronie Teaching Hospital, 34295 Montpellier cedex 5, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Morel
authors.affiliation: Rheumatology Department, Hautepierre Teaching Hospital, 67098 Strasbourg cedex, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.affiliation: Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Jamard
authors.affiliation: INSERM, UMR1027, 31062 Toulouse cedex 9, France; Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cambon-Thomsen
authors.affiliation: Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France; Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France; Inserm UMR 1043, CPTP Toulouse Purpan, BP 3028, 31024 Toulouse cedex 3, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Cantagrel
authors.affiliation: Rheumatology Department, Claude Bernard-Bichat Teaching Hospital, Paris VII University, 75890 Paris cedex 18, France; Paris VII University, 75890 Paris cedex 18, France; INSERM U699, 75890 Paris cedex 18, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieudé
authors.affiliation: INSERM, UMR1027, 31062 Toulouse cedex 9, France; Université de Toulouse III, UMR1027, 31062 Toulouse cedex 9, France; Rheumatology Center, Purpan Teaching Hospital, CHU Toulouse, 1 place du Dr-Baylac, 31059 Toulouse cedex 9, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Constantin
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide
chemical_list: D001323:Autoantibodies; C508017:IL2RA protein, human; C508020:IL2RB protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Autoantibodies; Disease progression; IL-2RA; IL-2RB; Rheumatoid arthritis; Single nucleotid polymorphism