Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans

Abstract

Increased expression of interferon (IFN)-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). One transcription factor responsible for regulating IFN, interferon regulatory factor-5 (IRF5), has been associated with SLE in genetic studies of Asian, Caucasian and Hispanic populations. We genotyped up to seven polymorphic loci in or near IRF5 in a total of 4870 African-American and Caucasian subjects (1829 SLE sporadic cases and 3041 controls) from two independent studies. Population-based case-control comparisons were performed using the Pearson's w 2 -test statistics and haplotypes were inferred using HaploView. We observed significant novel associations with the IRF5 variants rs2004640 and rs3807306 in African Americans and replicated previously reported associations in Caucasians. While we identified risk haplotypes, the majority of haplotypic effects were accounted for by one SNP (rs3807306) in conditional analyses. We conclude that genetic variants of IRF5 associate with SLE in multiple populations, providing evidence that IRF5 is likely to be a crucial component in SLE pathogenesis among multiple ethnic groups.

Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjögren's syndrome

“…16 Whereas STAT4 has been associated with rheumatic diseases in patients of Caucasian and Asian origin, polymorphisms in IRF5 have been associated with SLE in multiple ethnic populations, including Hispanics and African Americans. 23,22,24 This implies that both IRF5 and STAT4 and the type I IFN system are of importance in the development of autoimmune rheumatic diseases.…”

Genetic association and interaction between the IRF5 and TYK2 genes and systemic lupus erythematosus in the Han Chinese population

“…Furthermore, a large-scale meta-analysis has detected a significant genetic association of TYK2 SNPs (rs34536443 and rs2304256) with autoimmune and inflammatory diseases [10]. For IRF5, another type I IFN gene, which encodes IFN regulatory factor 5 (IRF- 5), has been reported to be associated with SLE in Caucasian, African American, Korean and Japanese populations [11][12][13][14]. And subsequent detailed analyses revealed a SLE-risk haplotype [exon6(in)-rs10954213A-rs2004640T-rs2070197C] in Caucasian populations, but not in Asians [15].…”

The TLR and IL-1 signalling network at a glance

“…IRF5 is also a susceptibility factor associated with increase risk of lupus in humans (e.g. Graham et al, 2006;Graham et al, 2007;Kelly et al, 2008), a disease linked to the overproduction of type 1 IFNs by pDCs (Barrat et al, 2005). IRF7 Uematsu et al, 2005) and IRF5 (Steinhagen et al, 2013) undergo translocation from the cytosol to the nucleus in response to TLR7 or TLR9 agonists in pDCs, which might underlie their activation.…”