Interferon III-related IL28RA variant is associated with rheumatoid arthritis and systemic lupus erythematosus and specific disease sub-phenotypes

Int J Rheum Dis. 2021 Jan;24(1):49-55. doi: 10.1111/1756-185X.14015. Epub 2020 Dec 2.

Abstract

Background: The interferon pathways have been commonly implicated in autoimmune disease development but the identity of the genes involved has not yet been fully clarified. Variation in genes involved in interferon pathways is expected to have a role in the etiology of these diseases.

Methods: The potential association of a polymorphism in the IL28RA gene, involved in these pathways, with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and disease-related phenotypes was investigated in 603 Brazilian individuals (354 well-characterized SLE and RA patients, and 249 controls). IL28RA (rs4649203) variant was genotyped by TaqMan assay. Statistical analysis was performed including both diseases and a comprehensive list of patient clinical manifestations.

Results: The rs4649203-G (minor) allele was associated with SLE and RA occurrence and was shown to be a risk factor for serositis and anemia among SLE patients as well as a protective factor for rheumatoid vasculitis and rheumatoid nodules in RA patients, suggesting an association with a milder form of the disease.

Conclusions: The IL28RA gene may contribute to SLE and RA susceptibility and to specific clinical manifestations of the diseases.

Keywords: IL28RA; autoimmune disease; genetic association; interferon pathway; rheumatoid arthritis; systemic lupus erythematosus.

MeSH terms

  • Adolescent
  • Adult
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / immunology
  • Case-Control Studies
  • Disease Progression
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Receptors, Interferon / genetics*
  • Risk Assessment
  • Risk Factors
  • Young Adult

Substances

  • IFNLR1 protein, human
  • Receptors, Interferon