The decreased expression of IKBKE in systemic lupus erythematosus
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Published:2020-03-07
Issue:9
Volume:39
Page:2611-2617
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ISSN:0770-3198
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Container-title:Clinical Rheumatology
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language:en
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Short-container-title:Clin Rheumatol
Author:
Zhu Tingting, Hong Jiaqi, Shuai Zongwen, Xu Shengqian, Qian Danfeng, Hong Xiaojie, Liu Yaoguang, Chen Min, Meng Ziyuan, Zheng Lijun, Zheng Danlin, Zhang Xuejun, Liu LuORCID
Abstract
Abstract
Objective
The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE.
Methods
We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms.
Results
The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients.
Conclusion
In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals.
Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.
Funder
the National Key Laboratory Breeding Base of Dermatology of China the Key Laboratory of Dermatology Ministry of Education of China the Cultivation of fund winners of innovative research groups
Publisher
Springer Science and Business Media LLC
Subject
General Medicine,Rheumatology
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