Integration of major histocompatibility complex, methylation, and transcribed ultra-conserved regions analyses in uremia

Treatment of uremia is now dominated by dialysis, in some cases, patients are treated with dialysis for decades, but overall outcomes are disappointing. A number of studies have confirmed the relevance of several experimental insights to the pathogenesis of uremia, but the specific biomarkers of uremia have not been fully elucidated. A total of 15 uremia patients and 15 healthy controls were collected in the present study. The aim of this study was to explain the etiology of uremia, MHC gene capture technology, hMeDIP-chip, T-UCR microarray and bioinformatics analysis were utilised in the uremia and normal control group. The result showed 8 CpG methylated enrichment in MHC segment. We found 1 SNP in CpG promoter of lncRNA and 1 SNP in chr6: 28890951-28892013, 1 SNP in CpG chr6:29521110-29521833 and 1 SNP in CpG chr6:30684836-30685503. The CpG methylated corresponding gene wasn’t found significant immune correlated process GO term and KEGG pathway enrichment in uremia. In this experiment, T-UCR was not discovered in MHC segment. The T-UCR corresponding gene wasn’t found significant immune correlated process GO term and KEGG pathway enrichment too. Analysis of SNP (rs2301754, rs11545587, rs17184255, rs4713354) and expression of the gene in peripheral blood lymphocytes indicated these SNP were associated with the occurrence of uremia. Future studies should examine the roles of these SNP in the pathogenesis of uremia. Integrative analysis technology provided an expansive view of molecular signaling pathways in uremia. Introduction Uremia refers to the condition that occurs when kidney function regresses during chronic kidney disease. Chronic kidney disease represents the progressive loss of renal function, and its latest stageuremia, where little or no kidney function is present, requires either transplantation or dialysis [1]. In all stages of the disease, but particularly in uremia, patients present a many-fold increased mortality rate for cardiovascular disease than the general population. Despite intensive research, the pathologic mechanisms of uremia phenotype are still not completely understood and are probably multifactorial. Both genetic and environmental factors have been associated with uremia phenotype, but these factors cannot entirely explain the onset of uremia phenotype. Further studies are still encouraged to shed light on the true associations between uremia and its susceptibility genes. Novel methods should be looked into in this area. Using a predictive bioinformatics algorithm, Mantila Roosa et al. created a linear model of gene expression and identified 44 transcription factor binding motifs and 29 miRNA binding sites that were predicted to regulate gene expression across the time course. Known and novel transcription factor binding motifs were identified throughout the time course, as were several novel miRNA binding sites. These timedependent regulatory mechanisms may be important in controlling the loading-induced bone formation process [2]. This integrated bioinformatics analysis method may be looked into in our study. The link between MHC and uremia still unclear. Further investigations are likely to reveal the involvement of MHC in uremia. We are interested in studying MHC, CpG methylated and T-UCR as a first step toward better understanding regulation of gene expression in uremia. We report an expansive view of uremia from an integrated bioinformatics analysis of MHC, CpG methylated and T-UCR data sets. Materials and methods Human subjects Thirty subjects were enrolled in the study including 15 uremia patients on dialysis and 15 healthy volunteers. All uremia patients were recruited from the inpatient unit in the Department of Nephrology in the181st Hospital and were free of active infections, diabetes mellitus, and autoimmune diseases. Written informed consent was obtained from all the subjects or their guardians. The local Ethics Committee approved the study, and peripheral blood samples were obtained with informed consent from all Correspondence to: Yong Dai, Clinical Medical Research Center, The Second Clinical Medical College of Jinan University (Shenzhen People’s Hospital), 5518020, Shenzhen, Guangdong, People’s Republic of China, Fax: +86-75525626750; E-mail: [email protected]