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Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes
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 suscepti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008139/ https://www.ncbi.nlm.nih.gov/pubmed/33796098 http://dx.doi.org/10.3389/fimmu.2021.611515 |
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author | Zhu, Tingting Huang, Yuandi Qian, Danfeng Sheng, Yuming Zhang, Chaowen Chen, Shirui Zhang, Hui Wang, Hui Zhang, Xuejun Liu, Junlin Ding, Changhai Liu, Lu |
author_facet | Zhu, Tingting Huang, Yuandi Qian, Danfeng Sheng, Yuming Zhang, Chaowen Chen, Shirui Zhang, Hui Wang, Hui Zhang, Xuejun Liu, Junlin Ding, Changhai Liu, Lu |
author_sort | Zhu, Tingting |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8008139 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80081392021-03-31 Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes Zhu, Tingting Huang, Yuandi Qian, Danfeng Sheng, Yuming Zhang, Chaowen Chen, Shirui Zhang, Hui Wang, Hui Zhang, Xuejun Liu, Junlin Ding, Changhai Liu, Lu Front Immunol Immunology 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. Frontiers Media S.A. 2021-03-16 /pmc/articles/PMC8008139/ /pubmed/33796098 http://dx.doi.org/10.3389/fimmu.2021.611515 Text en Copyright © 2021 Zhu, Huang, Qian, Sheng, Zhang, Chen, Zhang, Wang, Zhang, Liu, Ding and Liu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Zhu, Tingting Huang, Yuandi Qian, Danfeng Sheng, Yuming Zhang, Chaowen Chen, Shirui Zhang, Hui Wang, Hui Zhang, Xuejun Liu, Junlin Ding, Changhai Liu, Lu Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title | Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title_full | Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title_fullStr | Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title_full_unstemmed | Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title_short | Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes |
title_sort | assessing the function of the zfp90 variant rs1170426 in sle and the association between sle drug target and susceptibility genes |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008139/ https://www.ncbi.nlm.nih.gov/pubmed/33796098 http://dx.doi.org/10.3389/fimmu.2021.611515 |
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