Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastable epialleles (MEs) are mammalian genomic loci where epigenetic patterning occurs before gastrulation in a stochastic fashion leading to systematic interindividual variation within one species. Importantly, periconceptual nutritional influences may modulate the establishment of epigenetic changes, such as DNA methylation at MEs. Based on these characteristics, we exploited Infinium HumanMethylation450 BeadChip kits in a 2-tissue parallel screen on peripheral blood leukocyte and colonic mucosal DNA from 10 children without identifiable large intestinal disease. This approach led to the delineation of 1776 CpG sites meeting our criteria for MEs, which associated with 1013 genes. The list of ME candidates exhibited overlaps with recently identified human genes (including CYP2E1 and MGMT, where methylation has been associated with Parkinson disease and glioblastoma, respectively) in which perinatal DNA methylation levels where linked to maternal periconceptual nutrition. One hundred 18 (11.6%) of the ME candidates overlapped with genes where DNA methylation correlated (r > 0.871; p < 0.055) with expression in the colon mucosa of 5 independent control children. Genes involved in homophilic cell adhesion (including cadherin-associated genes) and developmental processes were significantly overrepresented in association with MEs. Additional filtering of gene expression-correlated MEs defined 35 genes, associated with 2 or more CpG sites within a 10 kb genomic region, fulfilling the ME criteria. DNA methylation changes at a number of these genes have been linked to various forms of human disease, including cancers, such as asthma and acute myeloid leukemia (ALOX12), gastric cancer (EBF3), breast cancer (NAV1), colon cancer and acute lymphoid leukemia (KCNK15), Wilms tumor (protocadherin gene cluster; PCDHAs) and colorectal cancer (TCERG1L), suggesting a potential etiologic role for MEs in tumorigenesis and underscoring the possible developmental origins of these malignancies. The presented compendium of ME candidates may accelerate our understanding of the epigenetic origins of common human disorders.
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PMID:Human metastable epiallele candidates link to common disorders. 2332 99

The purpose of this study was to explore the key mechanism involved in the pathogenesis of Parkinson's disease (PD) based on microarray analysis. The expression profile data of GSE7621, which contained 9 substantia nigra tissues isolated from normals and 16 substantia nigra tissues isolated from PD patients, was obtained from Gene Expression Omnibus. The differentially expressed genes (DEGs) were screened, followed by functional enrichment analysis and protein-protein interaction (PPI) network construction. After the miRNAs regulating the DEGs were predicted, the miRNA-DEG regulatory network was then constructed. Besides, the 6-hydroxydopamine rat model of PD was established and the expression of key DEGs and miRNA was detected. A total of 388 DEGs were identified, including 218 upregulated genes and 170 downregulated ones. Tyrosine hydroxylase (TH) and solute carrier family 6 member 3 (SLC6A3) were significantly related to the functional terms of catecholamine biosynthetic process and dopamine biosynthetic process. TH and SLC6A3 were hub nodes in the PPI network. EBF3 could be targeted by miR-218. Moreover, TH and SLC6A3 were found downregulated in the 6-OHDA rat model of PD, while miR-218 was markedly upregulated. Our results reveal that SLC6A3, TH, and EBF3 targeted by miR-218 could be involved in PD. These molecules might provide a new insight into the development of therapeutic strategies for PD.
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PMID:Identification of Critical Genes and miRNAs Associated with the Development of Parkinson's Disease. 3008 84