title: The role of genetic variation near interferon-kappa in systemic lupus erythematosus.
abstract: 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.
authors: Division of Molecular Immunology and Graduate Program in Immunobiology, Cincinnati Children's Hospital Research Foundation, OH 45267, USA.
authors: Isaac T W
authors: IT
authors: Harley
authors: Timothy B
authors: TB
authors: Niewold
authors: Rebecca M
authors: RM
authors: Stormont
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Stuart B
authors: SB
authors: Glenn
authors: Beverly S
authors: BS
authors: Franek
authors: Jennifer A
authors: JA
authors: Kelly
authors: Jeffrey R
authors: JR
authors: Kilpatrick
authors: David
authors: D
authors: Hutchings
authors: Jasmin
authors: J
authors: Divers
authors: Gail R
authors: GR
authors: Bruner
authors: Jeffrey C
authors: JC
authors: Edberg
authors: Gerald
authors: G
authors: McGwin
authors: Michelle A
authors: MA
authors: Petri
authors: Rosalind
authors: R
authors: Ramsey-Goldman
authors: John D
authors: JD
authors: Reveille
authors: Luis M
authors: LM
authors: Vilá-Pérez
authors: Joan T
authors: JT
authors: Merrill
authors: Gary S
authors: GS
authors: Gilkeson
authors: Timothy J
authors: TJ
authors: Vyse
authors: Marta E
authors: ME
authors: Alarcón-Riquelme
authors: Soo-Kyung
authors: SK
authors: Cho
authors: Chaim O
authors: CO
authors: Jacob
authors: Graciela S
authors: GS
authors: Alarcón
authors: Kathy L
authors: KL
authors: Moser
authors: Patrick M
authors: PM
authors: Gaffney
authors: Robert P
authors: RP
authors: Kimberly
authors: Sang-Cheol
authors: SC
authors: Bae
authors: Carl D
authors: CD
authors: Langefeld
authors: John B
authors: JB
authors: Harley
authors: Joel M
authors: JM
authors: Guthridge
authors: Judith A
authors: JA
authors: James
mesh_terms: D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012879:Skin Physiological Phenomena; D018709:Statistics, Nonparametric
chemical_list: D007370:Interferon Type I; C439669:interferon kappa