The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus

نویسندگان

  • Isaac T. W. Harley
  • Timothy B. Niewold
  • Rebecca M. Stormont
  • Kenneth M. Kaufman
  • Stuart B. Glenn
  • Beverly S. Franek
  • Jennifer A. Kelly
  • Jeffrey R. Kilpatrick
  • David Hutchings
  • Jasmin Divers
  • Gail R. Bruner
  • Jeffrey C. Edberg
  • Gerald McGwin
  • Michelle A. Petri
  • Rosalind Ramsey-Goldman
  • John D. Reveille
  • Luis M. Vilá-Pérez
  • Joan T. Merrill
  • Gary S. Gilkeson
  • Timothy J. Vyse
  • Marta E. Alarcón-Riquelme
  • Soo-Kyung Cho
  • Chaim O. Jacob
  • Graciela S. Alarcón
  • Kathy L. Moser
  • Patrick M. Gaffney
  • Robert P. Kimberly
  • Sang-Cheol Bae
  • Carl D. Langefeld
  • John B. Harley
  • Joel M. Guthridge
  • Judith A. James
چکیده

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.

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عنوان ژورنال:

دوره 2010  شماره 

صفحات  -

تاریخ انتشار 2010