The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus
The Role of Genetic Variation Near Interferon-Kappa in Systemic Lupus Erythematosus
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DOI：
10.1155/2010/706825
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发表时间：
2010-01-01
影响因子：
--
通讯作者：
James, Judith A.
中科院分区：
文献类型：
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作者：
Harley, Isaac T. W.;Niewold, Timothy B.;James, Judith A.
系统性红斑狼疮（SLE）是一种全身性自身免疫性疾病，其特征是I型干扰素（IFN）增加和多器官炎症，经常靶向皮肤。IFN-κ是在皮肤中表达的I型IFN。一项合并的全基因组扫描显示IFNK基因座与SLE易感性有关。我们研究了IFNK单核苷酸多态性（SNPs）在3982例SLE患者和4275名对照，包括欧洲（EA），非洲裔美国人（AA），和亚洲血统。rs 12553951 C与EA男性的SLE相关（比值比= 1.93，P = 2.5 x 10（-4）），但与女性无关。提示协会与皮肤表型EA和AA女性被发现，这些也是性别特异性的。IFNK单核苷酸多态性与EA和AA SLE患者血清I型IFN水平升高相关。我们的数据表明IFNK单核苷酸多态性与SLE和皮肤表型之间存在性别依赖性关联。血清IFN相关性表明IFNK变体可能影响受影响皮肤中产生I型IFN的浆细胞样树突状细胞。
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.