Demirci F Y K, Manzi S, Ramsey-Goldman R, Minster R L, Kenney M, Shaw P S, Dunlop-Thomas C M, Kao A H, Rhew E, Bontempo F, Kammerer C, Kamboh M I
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Ann Hum Genet. 2007 May;71(Pt 3):308-11. doi: 10.1111/j.1469-1809.2006.00336.x. Epub 2006 Dec 12.
Interferon regulatory factor 5 (IRF5) belongs to a family of transcription factors that control the transactivation of type I interferon system-related genes, as well as the expression of several other genes involved in immune response, cell signalling, cell cycle control and apoptosis. Two recent studies reported a significant association between the IRF5/rs2004640 T allele and systemic lupus erythematosus (SLE). The purpose of this study was to determine whether the reported rs2004640 T allele association could be replicated in our independent SLE case-control sample. We genotyped DNA samples from 370 white SLE-affected female subjects and 462 white healthy female controls using the TaqMan Assay-on-Demand for rs2004640, and performed a case-control genetic association analysis. Frequency of the rs2004640 T allele was significantly higher in cases than in controls (56.5% vs. 50%; P= 0.008). The odds ratio for T allele carriers was 1.68 (95% CI: 1.20 - 2.34; P= 0.003). Our results in an independent case-control sample confirm the robust association of the IRF5/rs2004640 T allele with SLE risk, and further support the relevance of the type I interferon system in the pathogenesis of SLE and autoimmunity.
干扰素调节因子5（IRF5）属于转录因子家族，可控制I型干扰素系统相关基因的反式激活，以及参与免疫反应、细胞信号传导、细胞周期调控和细胞凋亡的其他几个基因的表达。最近的两项研究报告称，IRF5/rs2004640 T等位基因与系统性红斑狼疮（SLE）之间存在显著关联。本研究的目的是确定所报道的rs2004640 T等位基因关联是否能在我们独立的SLE病例对照样本中得到重复验证。我们使用TaqMan按需检测法对rs2004640对370名患SLE的白人女性受试者和462名白人健康女性对照的DNA样本进行基因分型，并进行了病例对照基因关联分析。rs2004640 T等位基因在病例中的频率显著高于对照（56.5%对50%；P = 0.008）。T等位基因携带者的优势比为1.68（95%置信区间：1.20 - 2.34；P = 0.003）。我们在独立病例对照样本中的结果证实了IRF5/rs2004640 T等位基因与SLE风险之间的密切关联，并进一步支持了I型干扰素系统在SLE发病机制和自身免疫中的相关性。
