Assessing the Function of the ZFP90 Variant rs1170426 in SLE and the Association Between SLE Drug Target and Susceptibility Genes

Frontiers in Immunology

Danfeng Qian²  Hui Zhang³  Hui Wang³  Chaowen Zhang³  Yuandi Huang³  Yuming Sheng³  Shirui Chen³  Xuejun Zhang³  Junlin Liu⁴  Lu Liu⁵  Tingting Zhu⁶  Changhai Ding⁷ 

[1] Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Zhujiang, China;Department of Dermatology, Lu’an People’s Hospital, Lu’an, China;Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, China;Department of Dermatology, The Second Affiliated Hospital, Hainan Medical University, Haikou, China;Department of Medical and Molecular Genetics, King’s College London, London, United Kingdom;Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China;Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia;

关键词: ZFP90;    single nucleotide polymorphism;    systemic lupus erythematosus;    eQTL;    SLE drug target genes;   

DOI  :  10.3389/fimmu.2021.611515

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown