Background and aims Previous study identified rs1131665 in IRF7 associated with SLE among multiple ethnic groups. This study was undertaken to investigate whether other genetic polymorphisms within KIAA1542/IRF7 confers risk for the development of SLE.

Methods Four SNPs, including rs4963128, rs702966, rs1131665 (Q412R), rs1061502 (K179E) within KIAA1542/IRF7 were genotyped in 784 Chinese SLE patients and 899 controls/IRF7 by using Taqman genotyping assay. Luciferase reporter assay, Co-IP and EMSA were used to assess the effect of K179E polymorphism on the activation of IRF7.

Results Q412R and K179E were significantly associated with SLE in Chinese Han population (p=5.8X10^-3, OR=2.33[1.26–4.33], p=2.9X10^-3, OR=2.82[1.38–5.76], respectively. IRF7 3’UTR SNP rs702966 was associated with renal involvement (p=0.01 OR=0.46[0.25–0.85]. Compared with expression of IRF7 179E, expression of IRF7 179K risk allele resulted in a 4-fold increase in ISRE transcriptional activity and stronger ISRE binding activity in EMSA (p=0.0002), suggesting IRF7 179K confers elevated IRF7 activity. Further study found 179K (lysine) carrying IRF7 protein showed higher acetylation compared to 179 E (glutamic acid) IRF7.

Conclusions We detected a novel association between rs1061502 (K179E) and SLE susceptibility. K179E could change the acetylation of IRF7 in vitro, which might contribute to the transcriptional activity of IRF7.