The role of genetic variation near interferon-kappa in systemic lupus erythematosus.

Academic Article


  • Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility. We studied IFNK single nucleotide polymorphisms (SNPs) in 3982 SLE cases and 4275 controls, composed of European (EA), African-American (AA), and Asian ancestry. rs12553951C was associated with SLE in EA males (odds ratio = 1.93, P = 2.5 x 10(-4)), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. IFNK SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between IFNK SNPs and SLE and skin phenotypes. The serum IFN association suggests that IFNK variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.
  • Keywords

  • Case-Control Studies, Chi-Square Distribution, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Interferon Type I, Linkage Disequilibrium, Lupus Erythematosus, Systemic, Male, Phenotype, Polymorphism, Single Nucleotide, Sex Factors, Skin Physiological Phenomena, Statistics, Nonparametric
  • Digital Object Identifier (doi)

    Author List

  • Harley ITW; Niewold TB; Stormont RM; Kaufman KM; Glenn SB; Franek BS; Kelly JA; Kilpatrick JR; Hutchings D; Divers J
  • Volume

  • 2010