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)

Insulin-dependent diabetes mellitus (IDDM) is a T-cell-mediated autoimmune disease characterized by the destruction of insulin-producing beta cells in the islet of Langerhans. Islet autoantigen-specific T cells play a major role in the pathogenesis of the disease. Susceptibility loci for autoimmune diabetes such as the major histocompatability complex (MHC) may function by producing different repertoires of T cells, which could gain autoreactivity following activation, resulting in autoimmune disease. However, all the T cells infiltrating the islets are not destructive. A number of autoreactive T-cell lines capable of preventing development of IDDM have been isolated. Most of these cell lines are reactive to self I-Ag7. Presence of these regulatory T cells along with the effector cells in nonobese diabetic (NOD) mice suggests that IDDM may be a result of the imbalance of these two types of cells. Modulation of the immune response by inducing autoreactive regulatory T cells could be a way of treating autoimmune disorders.
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PMID:Modulation of insulin-dependent diabetes mellitus (IDDM) in NOD mice by autoreactive T cells. 941 39

Genetic studies have identified a number of loci demonstrating linkage to type 1 diabetes. One of the largest single contributors to genetic susceptibility, after the major histocompatability complex, is the IDDM2 locus, which maps to a nontranscribed variable number of tandem repeats (VNTR) minisatellite upstream of the insulin (INS) and insulin-like growth factor 2 (IGF2) genes. In a progression from population to functional studies, recent reports have shown that VNTR susceptibility alleles (class I) have different transcriptional effects on INS than protective VNTR alleles (class III) in thymus and pancreas, two tissues important in the pathogenesis of the disease. Similar VNTR transcriptional effects on IGF2 have also been proposed as a mechanism by which the IDDM2 locus confers susceptibility in addition to, or instead of, effects on INS. We evaluated this hypothesis by comparing IGF2 expression levels from chromosomes with the protective class III alleles to those with class I alleles in tissues relevant to type 1 diabetes pathogenesis. In thymus, class III alleles were associated with an IGF2 mRNA level of 4.7 +/- 0.9 (mean +/- SE, arbitrary units, n = 12) compared with 4.7 +/- 1.3 for class I alleles (n = 17). The same absence of a significant difference was found in pancreas, where class III alleles were associated with a level of 28.4 +/- 4.2 (n = 7) and class I alleles with a level of 29.5 +/- 5.2 (n = 6). There was a significant correlation between fetal age and IGF2 in both tissues, but fetal ages were not different in the genotype groups compared. We therefore did not detect any significant difference in IGF2 mRNA levels associated with the protective class of VNTR alleles as compared with the predisposing class. This is evidence against the hypotheses that have suggested IGF2 is a mediator of IDDM2-encoded susceptibility and corroborates previous studies suggesting insulin is the gene involved.
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PMID:A functional analysis of the role of IGF2 in IDDM2-encoded susceptibility to type 1 diabetes. 958 57

Genetic analysis of a mouse model of major histocompatability complex (MHC)-associated autoimmune type 1 (insulin-dependent) diabetes mellitus (IDDM) has shown that the disease is caused by a combination of a major effect at the MHC and at least ten other susceptibility loci elsewhere in the genome. A genome-wide scan of 93 affected sibpair families (ASP) from the UK (UK93) indicated a similar genetic basis for human type 1 diabetes, with the major genetic component at the MHC locus (IDDM1) explaining 34% of the familial clustering of the disease (lambda(s)=2.5; refs 3,4). In the present report, we have analysed a further 263 multiplex families from the same population (UK263) to provide a total UK data set of 356 ASP families (UK356). Only four regions of the genome outside IDDM1/MHC, which was still the only major locus detected, were not excluded at lambda(s)=3 and lod=-2, of which two showed evidence of linkage: chromosome 10p13-p11 (maximum lod score (MLS)=4.7, P=3x10(-6), lambda(s)=1.56) and chromosome 16q22-16q24 (MLS=3.4, P=6.5x10(-5), lambda(s)=1.6). These and other novel regions, including chromosome 14q12-q21 and chromosome 19p13-19q13, could potentially harbour disease loci but confirmation and fine mapping cannot be pursued effectively using conventional linkage analysis. Instead, more powerful linkage disequilibrium-based and haplotype mapping approaches must be used; such data is already emerging for several type 1 diabetes loci detected initially by linkage.
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PMID:A search for type 1 diabetes susceptibility genes in families from the United Kingdom. 966 86

The PTPN22 locus is one of the strongest risk factors outside of the major histocompatability complex that associates with autoimmune diseases. PTPN22 encodes lymphoid protein tyrosine phosphatase (Lyp) which is expressed exclusively in immune cells. A single base change in the coding region of this gene resulting in an arginine to tryptophan amino acid substitution within a polyproline binding motif associates with type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosis, Hashimotos thyroiditis, Graves disease, Addison's disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile idiopathic arthritis and psoriatic arthritis. Here, we review the current understanding of the PTPN22 locus from a genetic, geographical, biochemical and functional perspective.
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PMID:Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? 2151 66