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The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus
Harley, Isaac T. W.,Niewold, Timothy B.,Stormont, Rebecca M.,Kaufman, Kenneth M.,Glenn, Stuart B.,Franek, Beverly S.,Kelly, Jennifer A.,Kilpatrick, Jeffrey R.,Hutchings, David,Divers, Jasmin,Bruner, G Hindawi Publishing Corporation 2010 Journal of biomedicine & biotechnology Vol.2010 No.-
<P>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 <I>IFNK</I> locus in SLE susceptibility. We studied <I>IFNK</I> 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, <I>P</I> = 2.5 × 10<SUP>−4</SUP>), but not females. Suggestive associations with skin phenotypes in EA and AA females were found, and these were also sex-specific. <I>IFNK</I> SNPs were associated with increased serum type I IFN in EA and AA SLE patients. Our data suggest a sex-dependent association between <I>IFNK</I> SNPs and SLE and skin phenotypes. The serum IFN association suggests that <I>IFNK</I> variants could influence type I IFN producing plasmacytoid dendritic cells in affected skin.</P>