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)

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by autoimmune destruction of pancreatic beta cells. Genetic and environmental factors contribute in this disease. There is evidence that MHC class I chain-related gene (MIC-A) plays a role in the susceptibility to this and other autoimmune diseases. There are five alleles of the MIC-A gene, which consist of different repetitions of GCT. In particular, MIC-A alleles 5 and 5.1 (the former with five repetitions of GCT, the latter with five repetitions and one additional insertion of nucleotide G) have been found to be associated with susceptibility to and age at onset of T1DM. The aim of our study was to analyze the transmission of these MIC-A alleles to T1DM-affected offsprings in HBDI families. These are multiplex families with affected offsprings and unaffected parents. DNA samples were amplified for MIC-A using fluorescence-labeled primers and analyzed on an ABI prism DNA sequencer. The transmission of alleles was then analyzed using pedigrees of families also obtained from HBDI. We analyzed 78 families and found that MIC-A alleles 5 and 5.1 are present and transmitted more frequently than expected. Heterozygotic parents for MIC-A alleles 5 and 5.1 were excluded from the study. Our results suggest that MIC-A alleles 5 and 5.1 are associated with susceptibility to T1DM in family studies.
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PMID:MHC class I chain-related gene alleles 5 and 5.1 are transmitted more frequently to type 1 diabetes offspring in HBDI families. 1202 Nov 30

Insulin-dependent diabetes mellitus (IDDM) is one of the most common chronic diseases. It is an autoimmune, polygenic disease, associated with several genes on different chromosomes. The most important gene is human leukocyte antigen (HLA), also known as major histocompatibility complex (MHC), which is located on chromosome 6p21.3. HLA-DQ8/DR4 and DQ2/DR3 are positively associated with IDDM and DQ6 is negatively associated with IDDM in most Caucasian populations. The MICA gene is located in the MHC class I region and is expressed by monocytes, keratinocytes, and endothelial cells. Sequence determination of the MICA gene identifies 5 alleles with 4, 5, 6, and 9 repetitions of GCT or 5 repetitions of GCT with 1 additional insertion (GGCT), and the alleles are referred to as A4, A5, A5.1, A6, and A9. Analysis of allele distribution among 93 Latvian IDDM patients and 108 healthy controls showed that allele A5 of MICA is significantly increased in IDDM patients [33/93 (35%)] compared to healthy controls [22/108 (20%)] (OR = 2.15; P = 0.016). In conclusion, we believe that MICA may play an important role in the etiopathogenesis of IDDM.
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PMID:Microsatellite allele 5 of MHC class I chain-related gene a increases the risk for insulin-dependent diabetes mellitus in latvians. 1202 Nov 40

Autoimmune disorders such as type 1 diabetes (T1DM), celiac disease (CD), and Addison's disease (ADD) develop in individuals with genetic susceptibility that are exposed to environmental triggering factors not completely defined. Patients with an autoimmune disease (and their relatives) are at increased risk of developing another disorder, and this might be caused by a common genetic origin of autoimmunity; for example, HLA class II region in 6p21 shows a very strong association with most diseases. The aim of this study was to determine whether shared susceptibility markers extend from the central (DRB1) through the telomeric (MICA) HLA region. We analyzed three independent sets of families with one autoimmune disease, T1DM, CD, or ADD, and genotyped them for HLA-DRB1 and for the exon 5 GCT polymorphism of MICA. For HLA-DRB1, allele DRB1*0301 was the only one associated with risk for all three diseases; in the case of MICA, allele A9 was found to be the common protective allele. Haplotype analysis shows that haplotype A5.1-DRB1*0301 confers risk to autoimmunity. Our results show that there are common risk and protection alleles in both loci, suggesting a core of genetic association with autoimmunity (HLA-DRB1*0301 risk; A9 protection) that could be modulated by other alleles/loci or environmental factors toward one or another disease. Some alleles are part of conserved haplotypes (A5.1-DR3, A5.1-DR2), whereas others seem to have independent effect (A9) and support the idea of two independent loci in this region.
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PMID:HLA-DRB1 and MICA in autoimmunity: common associated alleles in autoimmune disorders. 1467 82

We report a 19-year-old woman who had a history of type 1 diabetes with recurrent glycogen accumulation in the liver. During her infantile period she presented with no hepatomegaly nor growth retardation. On admission she was diagnosed with diabetic ketoacidosis (DKA). She also had hepatomegaly and elevated transaminase levels, but these abnormalities had resolved after administration of insulin. However, 4 weeks after DKA marked hepatomegaly and elevated transaminases were reappeared with simultaneous hypoglycemia which suggested an impaired glycogenolysis in the extraordinary conditions. We supposed the partial deficiency of liver glycogen phosphorylase activity in this patient and analyzed the liver glycogen phosphorylase gene (PYGL). Deduced amino acid sequence of the PYGL in this patient was completely identical to that reported by Burwinkel et al. (Y15233), however, the nucleotide sequence of PYGL cDNA was heterozygous for substitutions at positions Asp339 (GAT to GAC) on exon 9 and Ala703 (GCT to GCC on exon 17, respectively. These SNPs were also screened in 51 Japanese normal subjects by PCR-based direct sequencing or PCR-RFLP method. The same genotype observed in this patient was detected in 2 of 51(3.9%) normal subjects. These results suggest that the structure of PYGL coding sequence in this patient is unlikely to account for her excessive liver glycogen accumulation. Further studies including genetic analysis on the promoter region of the gene are necessary to clarify the etiology of susceptibility to excessive liver glycogen storage in patients with type 1 diabetes.
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PMID:Intermittent and recurrent hepatomegaly due to glycogen storage in a patient with type 1 diabetes: genetic analysis of the liver glycogen phosphorylase gene (PYGL). 1522 30