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Assessing the function of the ZFP90 variant rs1170426 in SLE and the association between SLE drug target and susceptibility genes

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Zhu, T, Huang, Y, Qian, D, Sheng, Y, Zhang, C, Chen, S, Zhang, H, Wang, H, Zhang, X, Liu, J, Ding, C ORCID: 0000-0002-9479-730X and Liu, L 2021 , 'Assessing the function of the ZFP90 variant rs1170426 in SLE and the association between SLE drug target and susceptibility genes' , Frontiers in Immunology, vol. 12 , pp. 1-10 , doi: 10.3389/fimmu.2021.611515.

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Abstract

A genome-wide association study (GWAS) has discovered that a polymorphism in the ZFP90 gene is associated with systemic lupus erythematosus (SLE). In this study, we explored the candidate function of a ZFP90 variant (rs1170426) in the context of SLE and detected the relationship between SLE susceptible genes and SLE drug target genes. First, we investigated the regulatory role of rs1170426 on ZFP90 expression by expression quantitative trait loci (eQTL) analysis in peripheral blood mononuclear cells (PBMCs), T, B, and monocytes cells and annotated the regulatory function of rs1170426 using bioinformatic databases. Second, we compared the case-control difference in ZFP90 expression levels. Third, we analyzed the association of genotype and ZFP90 expression levels with SLE clinical characters. Last, we showed the interaction of SLE susceptibility genes with SLE drug target genes. Subjects with the risk allele "C" of rs1170426 had lower expression levels of ZFP90 in PBMCs (P = 0.006) and CD8+ T cells (P = 0.003) from controls. SLE cases also had lower expression levels compared with controls (P = 2.78E-9). After correction for multiple testing, the ZFP90 expression levels were related to serositis (FDR p = 0.004), arthritis (FDR p = 0.020), hematological involvement (FDR p = 0.021), and increased C-reactive protein (CRP) (FDR p = 0.005) in cases. Furthermore, the SLE susceptible genes and the recognized SLE drug target genes were more likely to act upon each other compared with non-SLE genetic genes (OR = 2.701, P = 1.80E-5). These findings suggest that ZFP90 might play a role in the pathogenesis of SLE, and SLE genetics would contribute to therapeutic drug discovery.

Item Type: Article
Authors/Creators:Zhu, T and Huang, Y and Qian, D and Sheng, Y and Zhang, C and Chen, S and Zhang, H and Wang, H and Zhang, X and Liu, J and Ding, C and Liu, L
Keywords: SLE drug target genes, ZFP90, eQTL, single nucleotide polymorphism, systemic lupus erythematosus
Journal or Publication Title: Frontiers in Immunology
Publisher: Frontiers Research Foundation
ISSN: 1664-3224
DOI / ID Number: 10.3389/fimmu.2021.611515
Copyright Information:

Copyright © 2021 Zhu, Huang, Qian, Sheng, Zhang, Chen, Zhang, Wang, Zhang, Liu,Ding and Liu. This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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