Study On MRNA Expression Of IKZF1 In Peripheral Blood Mononuclear Cells Of Sle Patients

Background Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems and organs. Its pathogenesis has not been entirely elucidated. SLE is a polygenic disease, which is related with genetic, immune, viral infections, drugs, hormones and so on. Genetic factors may play an important role in the pathogenesis of SLE. In the past two decades, many groups had identified susceptibility genes by genome-wide scanning and candidate gene study. However, most results were not consistent. Online Mendelian Inheritance in Man (OMIM) embodies 13 SLE susceptibility loci. There are 11 loci which have been found by linkage analysis and genome-wide scan: 1q41-42 (SLEB1), 2q37.3 (SLEB2), 4p16-15.2 (SLEB3), 12q24 (SLEB4), 13q32 (SLEB5), 16q11.2 (SLEB6), 20p12 (SLEB7), 20q13.1 (SLEB8), 1q32 (SLEB9), 7q32 (SLEB10), 2q32.2-q32.3 (SLEB11). We have found a number of susceptibility genes by fine mapping and candidate gene approach, including PTPN22, CRP, FCGR2A, FCGR3A, FCGR2B, STAT4, IRF5, TLR5, ITGAM-ITGAX, FAS, PARP, PDCD1, HLA-DRB1, C2 and C4.In recent years, as the international HapMap project has been finished and lower-cost, highly efficient and high-throughput genotyping technologies are appearing, genome-wide association study (GWAS) has become the most effective method to search for susceptibility genes of multifactorial disease. Recently, we have identified nine new susceptibility loci including IKZF1, (SNP rs4917014 association with SLE OR=0.72, 95% CI: 0.68-0.77, P=2.75×10-23) in Chinese Han population by GWAS. Biologically, the IKZF1gene encodes the lymphoid transcription factor Ikaros whose function is required for development of all lymphoid cells.Objective We study IKZF1 mRNA expression levels in peripheral blood mononuclear cells of SLE patients, and explore whether the IKZF1expression is associated with the variant of the SNP rs4917014 and SLEDAI.Methods Fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to examine the expression of IKZF1 mRNA in PBMCs in 60 SLE patients and 60 controls. Sequenom MassArray system was used to genotype single nucleotide polymorphism (rs4917014) in 60 case of SLE and 60 normal controls. The SPSS10.0 software was used for statistical analysis.Results The expression levels of IKZF1 mRNAs in SLE patients were significantly decreased than those in healthy controls (P < 0.01). No relationship was found between IKZF1 mRNA expression levels and SLEDAI scores or SNP rs4917014.Conclusion It suggests that expression of IKZF1 mRNA may be correlated with the pathogenesis of SLE.