RESUMO
Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that generally induces the progression of rapidly progressive glomerulonephritis (GN). The purpose of this study was to identify key biomarkers and immune-related pathways involved in the progression of ANCA-associated GN (ANCA-GN) and their relationship with immune cell infiltration. Methods: Gene microarray data were downloaded from the Gene Expression Omnibus (GEO). Hub markers for ANCA-GN were mined based on differential expression analysis, weighted gene co-expression network analysis (WGCNA) and lasso regression, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) of the differential genes. The infiltration levels of 28 immune cells in the expression profile and their relationship to hub gene markers were analysed using single-sample GSEA (ssGSEA). In addition, the accuracy of the hub markers in diagnosing ANCA-GN was subsequently evaluated using the receiver operating characteristic curve (ROC). Results: A total of 651 differential genes were screened. Twelve co-expression modules were obtained via WGCNA; of which, one hub module (black module) had the highest correlation with ANCA-GN. A total of 66 intersecting genes were acquired by combining differential genes. Five hub genes were subsequently obtained by lasso analysis as potential biomarkers for ANCA-GN. The immune infiltration results revealed the most significant relationship among monocytes, CD4+ T cells and CD8+ T cells. ROC curve analysis demonstrated a prime diagnostic value of the five hub genes. According to the functional enrichment analysis of the differential genes, hub genes were mainly enhanced in immune- and inflammation-related pathways. Conclusion: B cells and monocytes were closely associated with the pathogenesis of ANCA-GN. Hub genes (CYP3A5, SLC12A3, BGN, TAPBP and TMEM184B) may be involved in the progression of ANCA-GN through immune-related signal pathways.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/imunologia , Autoimunidade , Biomarcadores , Glomerulonefrite/etiologia , Glomerulonefrite/metabolismo , Transdução de Sinais , Animais , Doenças Autoimunes/etiologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Biologia Computacional/métodos , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Glomerulonefrite/patologia , Humanos , Curva ROC , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismoRESUMO
BACKGROUND: As indicated by numerous studies, there exists a relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) and susceptibility to diabetic nephropathy (DN) in various populations; nonetheless, the findings remain inconsistent. Therefore, we carried out a meta-analysis to determine the relationship between the MTHFR gene polymorphism and DN susceptibility. MATERIALS AND METHOD: Related studies were identified from PubMed, Cochrane Library, EMBASE, and the China National Knowledge Infrastructure database (time period: from building the library to October 2019). The strength of the association was examined using odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: The findings illustrated that the C677T gene polymorphism was significantly associated with an enhanced susceptibility to DN compared to that with diabetes mellitus in allelic (ORâ=â1.64, 95% CIâ=â1.34-2.00, Pâ<â.001), dominant (ORâ=â1.85, 95% CIâ=â1.40-2.46, Pâ<â.001), codominant (heterozygote: ORâ=â1.67, 95% CIâ=â1.27-2.21, Pâ<â.001; homozygote: ORâ=â2.55, 95% CIâ=â1.82-3.57, Pâ<â.001), and recessive (ORâ=â1.89, 95% CIâ=â1.50-2.38, Pâ<â.001) models of the overall population. Moreover, as compared with the healthy controls, a significantly augmented susceptibility to DN was found in all 5 genetic comparison models (allelic: ORâ=â2.06, 95% CIâ=â1.58-2.67, Pâ<â.001; dominant: ORâ=â2.52, 95% CIâ=â1.73-3.69, Pâ<â.001; codominant: ORâ=â3.78, 95% CIâ=â2.50-5.70, Pâ<â.001; recessive: ORâ=â2.41, 95% CIâ=â1.96-2.97, Pâ<â.001). Furthermore, stratifying data by ethnicity revealed substantially augmented vulnerability to DN in not only Caucasian but also Asian populations. CONCLUSION: The present study suggests that the C677T polymorphism was associated with an augmented susceptibility to DN.