Abstract
Primary Sjögren's syndrome (pSS) is a systematic autoimmune disease with evidence of genetic predisposition. The IKZF1 (IKAROS family zinc finger 1 (Ikaros)) gene is located at 7p12.2, encodes a transcription factor related to chromatin remodeling, regulates lymphocyte differentiation, and has been reported to be associated with some autoimmune diseases. However, there have been no reports of an association between IKZF1 and pSS. To investigate the possibility of an association between the IKZF1 locus and pSS, we selected two single nucleotide polymorphisms (SNPs) in the IKZF1 locus, rs4917129 and rs4917014, based on a detailed analysis of genome-wide association study (GWAS) data and performed genotyping in 665 Han Chinese pSS patients and 863 healthy controls. The results of an association test showed significant association signals (rs4917129: P-value = 5.5e-4, OR (odds ratio) = 0.72, 95% CI (confidence interval) = 0.60-0.87; rs4917014: P-value = 1.2e-3, OR = 0.76, 95% CI = 0.64-0.89). A meta-analysis that combined the above results with data from previous GWAS, further confirmed these associations (rs4917129: Pmeta = 4.24e-8, ORmeta = 0.70, 95% CI = 0.61-0.79; rs4917014: Pmeta = 6.0e-8, ORmeta = 0.72, 95% CI = 0.64-0.81). A bioinformatics analysis indicated that both SNPs were located in a putative enhancer area in immune-related cell lines and tissues. A protein-protein interaction analysis found that IKZF1, together with GTF2I (an SS susceptibility gene newly identified through GWAS), could interact with histone deacetylase family proteins. In summary, this is the first study to report an association between IKZF1 and SS in Han Chinese.