Systemic lupus erythematosus (SLE) is a chronic, potentially fatal systemic autoimmune disease characterized by the production of autoantibodies against a wide range of self-antigens. To investigate the role of the 5-hmC DNA modification with regard to the onset of SLE, we compared the levels 5-hmC between SLE patients and normal controls. Whole blood was obtained from patients, and genomic DNA was extracted. Using the hMeDIP-chip analysis and validation by quantitative RT-PCR (RT-qPCR), we identified the differentially hydroxymethylated regions that are associated with SLE. There were 1,701 genes with significantly different 5-hmC levels at the promoter region in the SLE patients compared with the normal controls. The CpG islands of 3,826 genes showed significantly different 5-hmC levels in the SLE patients compared with the normal controls. Out of the differentially hydroxymethylated genes, three were selected for validation, including TREX1, CDKN1A and CDKN1B. The hydroxymethylation levels of the three genes were confirmed by RT-qPCR. The results suggested that there were significant alterations of 5-hmC in SLE patients. Thus, these differentially hydroxymethylated genes may contribute to the pathogenesis of SLE. These findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based SLE therapies.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease which affects different organs and systems that, has a complex genetic inheritance, and is affected by both epigenetic and environmental risk factors. Previous studies on SLE have lacked the statistical power and genetic resolution to fully determine the influence of major histocompatibility complex (MHC) on SLE. In this study, in order to determine this influence, a total of 15 patients with SLE and 15 healthy controls were enrolled. MHC region capture technology, hMeDIP-chip, transcribed ultra-conserved region (T-UCR) microarray and bioinformatics analysis were utilized for both groups. The results revealed methylated CpG enrichment at 6 loci in the MHC segment of SLE. We found 4 single-nucleotide polymorphisms (SNPs) in the CpG promoter of human leukocyte antigen-B (HLA-B) and 2 SNPs in chr6:29521110‑29521833. No significant GO term or KEGG pathway enrichment was noted for an immune-correlated process in the SLE patients for the corresponding CpG-methylated genes. In this study, T-UCR was not discovered in the MHC segment. The analysis of SNPs (rs1050683, rs12697943, rs17881210, rs1065378, rs17184255 and rs16895070) and gene expression in peripheral blood lymphocytes indicated that these SNPs were associated with the occurrence of SLE. Further studies are warranted to examine the roles of these SNPs in the pathogenesis of SLE. Integrative analysis technology provided a view of the molecular signaling pathways in SLE.

Down syndrome (DS) is caused by trisomy of human chromosome 21 and is associated with a number of deleterious phenotypes. To investigate the role of microRNA (miRNA) in the regulation of DS, high-throughput Illumina sequencing technology and isobaric tagging for relative and absolute protein quantification analysis were utilized for simultaneous expression profiling of miRNA and protein in fetuses with DS and normal fetuses. A total of 344 miRNAs were associated with DS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to investigate the proteins found to be differentially expressed. Functionally important miRNAs were determined by identifying enriched or depleted targets in the transcript and the protein expression levels were consistent with miRNA regulation. The results indicated that GRB2, TMSB10, RUVBL2, the hsa-miR-329 and hsa-miR-27b, hsa-miR-27a targets, and MAPK1, PTPN11, ACTA2 and PTK2 or other differentially expressed proteins were connected with each other directly or indirectly. Integrative analysis of miRNAs and proteins provided an expansive view of the molecular signaling pathways in DS.

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Our studies indicate the significant alterations of 5-hmC. There is a correlation of gene modification 5-hmC in uremia patients. Such novel findings show the significance of 5-hmC as a potential biomarker or promising target for epigenetic-based uremia therapies.