Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, China.
Department of Rheumatology and Immunology, Arthritis Research Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Immunol. 2021 Mar 16;12:611515. doi: 10.3389/fimmu.2021.611515. eCollection 2021.
A genome-wide association study (GWAS) has discovered that a polymorphism in the gene is associated with systemic lupus erythematosus (SLE). In this study, we explored the candidate function of a 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 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 expression levels. Third, we analyzed the association of genotype and 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 in PBMCs ( = 0.006) and CD8+ T cells ( = 0.003) from controls. SLE cases also had lower expression levels compared with controls ( = 2.78E-9). After correction for multiple testing, the expression levels were related to serositis (FDR = 0.004), arthritis (FDR = 0.020), hematological involvement (FDR = 0.021), and increased C-reactive protein (CRP) (FDR = 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, = 1.80E-5). These findings suggest that might play a role in the pathogenesis of SLE, and SLE genetics would contribute to therapeutic drug discovery.
一项全基因组关联研究（GWAS）发现，基因中的一个多态性与系统性红斑狼疮（SLE）有关。在这项研究中，我们探讨了 SLE 背景下变体（rs1170426）的候选功能，并检测了 SLE 易感基因与 SLE 药物靶点基因之间的关系。首先，我们通过外周血单核细胞（PBMC）、T、B 和单核细胞中的表达数量性状基因座（eQTL）分析研究了 rs1170426 对表达的调控作用，并使用生物信息学数据库注释了 rs1170426 的调控功能。其次，我们比较了病例对照之间的表达水平差异。第三，我们分析了基因型和表达水平与 SLE 临床特征的关联。最后，我们展示了 SLE 易感基因与 SLE 药物靶点基因的相互作用。rs1170426 的风险等位基因“C”携带者在 PBMC（=0.006）和 CD8+T 细胞（=0.003）中的表达水平较低。SLE 病例与对照组相比表达水平也较低（=2.78E-9）。经多重检验校正后，表达水平与浆膜炎（FDR=0.004）、关节炎（FDR=0.020）、血液学受累（FDR=0.021）和 CRP 升高（FDR=0.005）有关。此外，与非 SLE 遗传基因相比，SLE 易感基因和公认的 SLE 药物靶点基因更有可能相互作用（OR=2.701，=1.80E-5）。这些发现表明，可能在 SLE 的发病机制中发挥作用，SLE 遗传学将有助于治疗药物的发现。
Zotero 插件
