| Background Systemic lupus erythematosus（SLE,OMIM 152700）is an autoimmune connective tissue system disease commonly found in women of childbearing age.Because of the destruction of immune tolerance,the formation of pathogenic autoantibodies and the abnormal elimination of immune complexes in the body lead to acute and chronic inflammation and eventually damage to multiple systems and organs.At present,the specific pathogenesis of SLE is still unclear,but many studies have shown that its pathogenesis is governed by genetic and environmental factors,of which genetics dominates.Non-genetic environmental factors include viral infections,bacterial infections,drugs,hormones,mental factors,sunlight,and ultraviolet light.To further investigate the genetic susceptibility of SLE,our team completed a large sample size genome-wide association（GWAS）meta-analysis in the early stage and found that the non-coding variant（rs2297550）located in the 1q32.1 IKBKE gene is closely related to SLE susceptibility.Objective To explore the effect of SNP rs2297550 on IKBKE gene expression and its relationship with clinical features and SLEDAI score.To study the relative expression and differential analysis of IKBKE gene in peripheral blood mononuclear cells（PBMCs）of SLE patients and healthy controls.We analyzed the influence of different genotypes and allele frequencies on the expression of IKBKE gene and its correlation with clinical manifestations of SLE.Methods First,we detected the regulatory effect of SNPs on gene expression and its impact on clinical characteristics by expression quantitative trait loci（e QTL）study.Then,we investigated IKBKE mRNA expression levels in PBMCs from 135 SLE patients and 130 healthy controls and its correlation with clinical features of patients using quantitative real-time PCR（q RT-PCR）,as well as the relationship between IKBKE mRNA expression and clinical characteristics in SLE patients.Finally,we further analysed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms.Results Compared with the healthy control group,the expression levels of IKBKE mRNA in patients with SLE were significantly decreased(P=2.32×10-12).Compared with SLE patients without vasculitis,IKBKE mRNA expression level was significantly decreased（P=0.015）.IKBKE mRNA expression level of SLE patients with elevated CRP was lower than that of patients with normal CRP（P=0.021）.However,no linear correlation between SLEDAI and gene expression was found.In the control group,SNP rs2297550 polymorphism was related to the expression level of IKBKE gene in PBMCs（P=0.022）,while there was no statistically significant difference between SNP rs2297550 polymorphism and IKBKE gene in PBMCs.The distribution of rs2297550genotypes in SLE cases was 34.7%,46.6%and 18.6%,respectively,and the distribution in healthy controls was 18.0%,55.5%and 26.7%.The G and C alleles of rs2297550 were 58.1%and 41.9%,respectively,in SLE cases and 54.3%and 45.7%,respectively,in healthy controls.There was no statistically significant difference in the distribution of rs2297550 genotypes and alleles in SLE cases and healthy controls.There was no significant statistical correlation between IKBKE gene polymorphism and the main clinical features of SLE.Conclusion In this study,we not only confirmed that the variant rs2297550 of IKBKE is closely related to SLE,but also proposed new functional hypotheses for the association signals.These findings suggest that IKBKE plays an important role in the pathogenesis of SLE.This provides the direction for the development of some new drugs and clinical interventions for systemic lupus erythematosus. |
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