Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

Joint Bone Spine. 2014 May;81(3):228-34. doi: 10.1016/j.jbspin.2013.10.002. Epub 2013 Nov 5.

Abstract

Objectives: 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.

Conclusion: A haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.

Keywords: Autoantibodies; Disease progression; IL-2RA; IL-2RB; Rheumatoid arthritis; Single nucleotid polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies
  • Cohort Studies
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes
  • Humans
  • Interleukin-2 Receptor alpha Subunit / genetics*
  • Interleukin-2 Receptor beta Subunit / genetics*
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology
  • Polymorphism, Single Nucleotide

Substances

  • Autoantibodies
  • IL2RA protein, human
  • IL2RB protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-2 Receptor beta Subunit
  • Peptides, Cyclic
  • cyclic citrullinated peptide