Bioinformatics analysis of epigenetic and SNP-related molecular markers in systemic lupus erythematosus.

We analyzed gene expression in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) using public databases. The goal was to identify lupus biomarkers by determining whether differentially expressed genes are mediated by methylation, miRNA, or SNP. Two cDNA microarrays were subjected to integration analysis, and we calculated the mutually differentially expressed genes (|log2fold change (FC)| > 1, P < 0.05). These genes were analyzed using gene otology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. The differences in methylation sites for two methylation chips were calculated and the differentially methylated sites were annotated. These genes were compared to the differentially expressed genes. We obtained 135 differentially expressed microRNAs from the microRNA-chip results using PBMCs from SLE and healthy individuals. Predictive microRNA target genes were identified using GO, KEGG pathways, and PPI networks. The target genes identified were compared to the differentially expressed genes. We downloaded Chinese SLE genome-wide association study data from SLE-related literature, analyzed the loci with a P value < 0.05, and used annotated SLE-associated SNPs. We selected the genes corresponding to an SNP located on an exon and determined the intersection with the differentially expressed genes. We found 18 differentially expressed genes in both cDNA microarrays. The methylation chips had 50 corresponding methylation sites. On the basis of these results, we identified two genes, IFI44 and IFI44L. We further identified 135 differentially expressed microRNAs predicted to affect 5766 target genes. Two identified genes were in common with the differentially expressed genes. Finally, SNP annotated genes and cDNA chip genes overlap with identified MX1. Therefore, we used existing data to analyze the causes of differential gene expression in SLE, introducing new methods for determining biomarkers and therapeutic targets.