Association of Interferon Regulatory Factor 5 (IRF5) polymorphisms with systemic lupus erythematosus (SLE)

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the dysfunction of immune cells, leading to hyperactivity of B cells and over-production of autoantibodies and the formation of immune complexes. The level of IFN-α, a type I interferon, is correlated with both SLE disease activity and severity, and is therefore suggested to be involved in the pathogenesis of SLE. Activation of transcription factors, including Interferon Regulatory Factors (IRFs) 3, 5 and 7 can modulate the expression of type I IFN genes. IRFs control inflammation, immunity and apoptosis. Irf5 knockout mouse also shows reduction of pro-inflammatory cytokines, including IL-6, IL-12 and TNF-a production. Recently several association studies in different populations have reported that IRF5 gene is a susceptibility gene of SLE. METHODS: We hypothesized that polymorphisms of IRF5 may affect the susceptibility and severity of SLE in the Hong Kong Chinese population. SNP rs2004640 creates a 5’ donor splice site for alternate isoform of transcript in exon 1, whereas rs10954213 creates a functional polyadenylation site in 3’ UTR and affects the expression of transcript variants. The 2 SNPs were genotyped in 444 SLE patients and 410 healthy controls, using sequencing. RESULTS: No association of IRF5 gene polymorphisms with SLE was found. However, an overall difference in the distribution of the haplotype frequencies between SLE patients and controls was detected. The haplotype TA was identified as a probable risk haplotypes associated with SLE