Min Wei1,2,3,4,5, Sijun Meng1,2,3,4,5, Sufang Shi1,2,3,4,5, Lijun Liu1,2,3,4,5, Xujie Zhou1,2,3,4,5, Jicheng Lv1,2,3,4,5, Li Zhu1,2,3,4,5, Hong Zhang1,2,3,4,5. 1. Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China. 2. Institute of Nephrology, Peking University, Beijing, China. 3. Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. 4. State Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. 5. Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Abstract
INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. It involves both genetic and environmental factors, among which DNA methylation, the most studied epigenetic modification, was shown to play a role. Here, we assessed genome-wide DNA methylation and gene expression profiles in 2 pairs of IgAN-discordant monozygotic (MZ) twins, in order to characterize methylation changes and their potential influences on gene expression in IgAN. METHODS: Genome-wide DNA methylation and gene expression profiles were evaluated in peripheral blood mononuclear cells obtained from 2 IgAN-discordant MZ twins. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected, and an integrated analysis was performed. Finally, functional enrichment analysis was done for DMR-associated genes and DEGs. RESULTS: Totally 521 DMRs were detected for 2 IgAN-discordant MZ twins. Among them, 9 DMRs were found to be mapped to genes that differentially expressed in 2 MZ twins, indicating the potential regulatory mechanisms of expression for these 9 genes (MNDA, DYSF, IL1R2, TLR6, TREML2, TREM1, IL32, S1PR5, and ADGRE3) in IgAN. Biological process analysis of them showed that they were mostly involved in the immune system process. Functional enrichment analysis of DEGs and DMR-associated genes both identified multiple pathways relevant to inflammatory and immune responses. And DMR-associated genes were significantly enriched in terms related to T-cell function. CONCLUSIONS: Our findings indicate that changes in DNA methylation patterns were involved in the pathogenesis of IgAN. Nine target genes detected in our study may provide new ideas for the exploration of molecular mechanisms of IgAN.
INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. It involves both genetic and environmental factors, among which DNA methylation, the most studied epigenetic modification, was shown to play a role. Here, we assessed genome-wide DNA methylation and gene expression profiles in 2 pairs of IgAN-discordant monozygotic (MZ) twins, in order to characterize methylation changes and their potential influences on gene expression in IgAN. METHODS: Genome-wide DNA methylation and gene expression profiles were evaluated in peripheral blood mononuclear cells obtained from 2 IgAN-discordant MZ twins. Differentially methylated regions (DMRs) and differentially expressed genes (DEGs) were detected, and an integrated analysis was performed. Finally, functional enrichment analysis was done for DMR-associated genes and DEGs. RESULTS: Totally 521 DMRs were detected for 2 IgAN-discordant MZ twins. Among them, 9 DMRs were found to be mapped to genes that differentially expressed in 2 MZ twins, indicating the potential regulatory mechanisms of expression for these 9 genes (MNDA, DYSF, IL1R2, TLR6, TREML2, TREM1, IL32, S1PR5, and ADGRE3) in IgAN. Biological process analysis of them showed that they were mostly involved in the immune system process. Functional enrichment analysis of DEGs and DMR-associated genes both identified multiple pathways relevant to inflammatory and immune responses. And DMR-associated genes were significantly enriched in terms related to T-cell function. CONCLUSIONS: Our findings indicate that changes in DNA methylation patterns were involved in the pathogenesis of IgAN. Nine target genes detected in our study may provide new ideas for the exploration of molecular mechanisms of IgAN.
Authors: Kar Neng Lai; Sydney C W Tang; Francesco Paolo Schena; Jan Novak; Yasuhiko Tomino; Agnes B Fogo; Richard J Glassock Journal: Nat Rev Dis Primers Date: 2016-02-11 Impact factor: 52.329
Authors: Fabio Sallustio; Grazia Serino; Sharon N Cox; Alessandra Dalla Gassa; Claudia Curci; Giuseppe De Palma; Barbara Banelli; Gianluigi Zaza; Massimo Romani; Francesco P Schena Journal: Clin Sci (Lond) Date: 2016-02-04 Impact factor: 6.124