The decreased expression of IKBKE in systemic lupus erythematosus
Open Access
- 7 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Clinical Rheumatology
- Vol. 39 (9), 2611-2617
- https://doi.org/10.1007/s10067-020-05006-6
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.Funding Information
- the National Key Laboratory Breeding Base of Dermatology of China (4601007103)
- the Key Laboratory of Dermatology Ministry of Education of China (4601007102)
- the Cultivation of fund winners of innovative research groups (4601011224)
This publication has 25 references indexed in Scilit:
- Contribution of IKBKE and IFIH1 gene variants to SLE susceptibilityGenes & Immunity, 2013
- HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variantsNucleic Acids Research, 2011
- A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLEEuropean Journal of Human Genetics, 2010
- Proteasome inhibitors prevent oxidative stress-induced nerve cell death by a novel mechanismBiochemical Pharmacology, 2008
- Tumour necrosis factor is expressed in refractory skin lesions from patients with subacute cutaneous lupus erythematosusAnnals Of The Rheumatic Diseases, 2006
- The two NF-κB activation pathways and their role in innate and adaptive immunityTrends in Immunology, 2004
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Human C-reactive protein: expression, structure, and functionMolecular Immunology, 2001
- Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosusArthritis & Rheumatism, 1997
- Derivation of the sledai. A disease activity index for lupus patientsArthritis & Rheumatism, 1992