Association of a Common Interferon Regulatory Factor 5 (IRF5) Variant with Increased Risk of Systemic Lupus Erythematosus (SLE)

Abstract

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.