Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We analyzed extended haplotypes composed of DNA loci on the short arm of chromosome 11 for segregation with insulin-dependent (type I) diabetes mellitus. The markers for these loci are tyrosine hydroxylase, insulin, and c-Ha-ras-1 proto-oncogene (HRAS1). We report, in a study of 27 families, that a specific haplotype (H), containing a 3-kilobase (kb) HRAS1-Taq I DNA polymorphism, segregated differentially in diabetic and nondiabetic siblings (P = 0.005). A parallel population study showed that the 3-kb HRAS1-Taq I polymorphism is increased in frequency in type I patients having two strong HLA-susceptibility haplotypes compared with other type I patients or healthy control blood donors (P less than 0.010 and P less than 0.025, respectively). The polymorphic variable, enhancer, and promoter regions flanking the human insulin gene on the H haplotype were not associated with type I diabetes. These results indicate that the HRAS1 locus or genes in linkage disequilibrium with this locus are involved in the pathogenesis of HLA-DR3/4 type I diabetes mellitus.
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PMID:Multigenic basis for type I diabetes. Association of HRAS1 polymorphism with HLA-DR3, DQw2/DR4, DQw8. 197 27

The linked polymorphic loci 5' to the insulin gene and 3' to the c-Harvey-ras-1 (c-Ha-ras) gene, both localised to the short arm of chromosome 11, have been studied in 14 type I diabetic pedigrees. The use of a cloned gene probe corresponding to the polymorphic locus adjacent to the insulin gene, in combination with the restriction endonuclease PvuII, has permitted an improvement in the resolution of sizes of insert at this locus. An MspI restriction fragment length polymorphism at the c-Ha-ras proto-oncogene locus (4 cM upstream from the insulin gene) was used to identify parental insulin gene related alleles unambiguously, and subsequently a pedigree analysis was performed to determine whether subclasses of inserts at this locus track with insulin dependent diabetes. Segregation analysis demonstrated no linkage between the polymorphic loci 5' to the insulin gene, nor 3' to the c-Ha-ras, and type I diabetes. However, a similar analysis confirmed an association between the HLA locus chromosome 6 and insulin dependent diabetes.
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PMID:DNA polymorphic haplotypes on the short arm of chromosome 11 and the inheritance of type I diabetes mellitus. 301 47

We have previously suggested that alterations in sequential early gene responses of trophic factors (IGF-1 -->c-fos-->NGF) contribute to impaired peripheral nerve regeneration in type 1 diabetic BB/W-rats. To study the role these responses may play in type 2 diabetic nerve regeneration, BB/Z-rats were subjected to sciatic nerve crush injury. The expression of IGF-1, c-fos, NGF and the receptors p75 and IGF-1R were determined at the protein and mRNA levels in sciatic nerve distal to the crush site by immunoblotting and semi-quantitative RT-PCR. In situ hybridization was performed to assess the cellular localization of IGF-1, NGF, p75, and IGF-1R mRNA and immunohistochemistry served to localize the source of p75 and IGF-1R protein expression. The data were compared to those of type 1 diabetic BB/Wor-rats and non-diabetic controls. Increased expression of IGF-1 in Schwann cells is the first growth factor response to injury and peaked at 0.5 hours (h) in control, 2 h in type 2 rats, and 24 h in type 1 rats. IGF-1R was expressed in Schwann cells and its expression was asynchronous to IGF-1 expression in type 1 rats but remained synchronous with IGF-1 in control and type 2 animals. The expression of the immediate early proto-oncogene c-fos exhibited an initial peak at 6 h in control animals, 24 h in type 2, and 2 days (d) in type 1 animals. The initial peak of NGF expression occurred at 6 h in non-diabetic rats, 24 h in type 2, and 2 d in type 1 diabetic rats. The expression of p75 was delayed and attenuated in type 1 diabetic rats; however, in type 2 diabetic rats it was similar to that of non-diabetic rats. These data indicate that early gene responses following nerve damage are significantly less perturbed in type 2 compared to type 1 diabetes. These differences may account for the more efficient nerve regeneration seen in type 2 diabetic polyneuropathy.
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PMID:Early gene responses of trophic factors in nerve regeneration differ in experimental type 1 and type 2 diabetic polyneuropathies. 1238 52

Differentially methylated genes (DMGs) serve a crucial role in the pathogenesis of glioma via the regulation of the cell cycle, proliferation, apoptosis, migration, infiltration, DNA repair and signaling pathways. This study aimed to identify aberrant DMGs and pathways by comprehensive bioinformatics analysis. The gene expression profile of GSE28094 was downloaded from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to find DMGs. Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of the DMGs were performed by using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed with Search Tool for the Retrieval of Interacting Genes. Analysis of modules in the PPI networks was performed by Molecular Complex Detection in Cytoscape software, and four modules were performed. The hub genes with a high degree of connectivity were verified by The Cancer Genome Atlas database. A total of 349 DMGs, including 167 hypermethylation genes, were enriched in biological processes of negative and positive regulation of cell proliferation and positive regulation of transcription from RNA polymerase II promoter. Pathway analysis enrichment revealed that cancer regulated the pluripotency of stem cells and the PI3K-AKT signaling pathway, whereas 182 hypomethylated genes were enriched in biological processes of immune response, cellular response to lipopolysaccharide and peptidyl-tyrosine phosphorylation. Pathway enrichment analysis revealed cytokine-cytokine receptor interaction, type I diabetes mellitus and TNF signaling pathway. A total of 20 hub genes were identified, of which eight genes were associated with survival, including notch receptor 1 (NOTCH1), SRC proto-oncogene (also known as non-receptor tyrosine kinase, SRC), interleukin 6 (IL6), matrix metallopeptidase 9 (MMP9), interleukin 10 (IL10), caspase 3 (CASP3), erb-b2 receptor tyrosine kinase 2 (ERBB2) and epidermal growth factor (EGF). Therefore, bioinformatics analysis identified a series of core DMGs and pathways in glioma. The results of the present study may facilitate the assessment of the tumorigenicity and progression of glioma. Furthermore, the significant DMGs may provide potential methylation-based biomarkers for the precise diagnosis and targeted treatment of glioma.
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PMID:Identification of core differentially methylated genes in glioma. 3178 78