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Journal Article
Research Support, Non-U.S. Gov't
Integrated analyses of a major histocompatibility complex, methylation and transcribed ultra-conserved regions in systemic lupus erythematosus.
International Journal of Molecular Medicine 2016 January
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.
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