Dataset Information

The decreased expression of IKBKE in systemic lupus erythematosus.

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.

SUBMITTER: Zhu T

PROVIDER: S-EPMC7426285 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

The decreased expression of IKBKE in systemic lupus erythematosus.

Zhu Tingting T Hong Jiaqi J Shuai Zongwen Z Xu Shengqian S Qian Danfeng D Hong Xiaojie X Liu Yaoguang Y Chen Min M Meng Ziyuan Z Zheng Lijun L Zheng Danlin D Zhang Xuejun X Liu Lu L

Clinical rheumatology 20200307 9

<h4>Objective</h4>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.<h4>Methods</h4>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 peripher ...[more]

PMID: 32146614

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Project description:ObjectiveTo evaluate the specificity of expression patterns of cell-free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).MethodsTotal RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcription-polymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.ResultsSeven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA-142-3p (miR-142-3p) and miR-181a was increased, and the expression of miR-106a, miR-17, miR-20a, miR-203, and miR-92a was decreased. In addition, the expression of miR-342-3p, miR-223, and miR-20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 × 10(-9) ). Use of the 4-miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.ConclusionCirculating miRNAs are systematically altered in SLE. A 4-miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor β signaling pathways. Other targets include regulation of apoptosis, cytokine-cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.

Dataset Information

The decreased expression of IKBKE in systemic lupus erythematosus.

Objective

Methods

Results

Conclusion

Publications

The decreased expression of IKBKE in systemic lupus erythematosus.

Similar Datasets

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