Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Tingting, Huang, Yuandi, Qian, Danfeng, Sheng, Yuming, Zhang, Chaowen, Chen, Shirui, Zhang, Hui, Wang, Hui, Zhang, Xuejun, Liu, Junlin, Ding, Changhai, Liu, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783672638842863616
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
work_keys_str_mv AT zhutingting assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT huangyuandi assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT qiandanfeng assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT shengyuming assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT zhangchaowen assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT chenshirui assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT zhanghui assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT wanghui assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT zhangxuejun assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT liujunlin assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT dingchanghai assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes
AT liulu assessingthefunctionofthezfp90variantrs1170426insleandtheassociationbetweensledrugtargetandsusceptibilitygenes