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

Our knowledge of the genetics of insulin dependent diabetes (IDDM), and in particular the HLA system, has gained considerable expansion thanks to the application of molecular biology. The genetic susceptibility to the disease is linked to the HLA region, particularly at DQ-alpha and DQ-beta chain genes. Particular amino acid other than aspartic acid in position 57 of the DQ beta chain and the presence of an arginine in position 52 of the DQ alpha chain and to how these markers can be used to identify subjects at risk for developing IDDM. The identification of such subjects may be useful for the development of strategies aimed to prevent the disease and in addition may offer a new insight into population screening.
 ...
PMID:The HLA system and insulin dependent diabetes: recent findings and prospects for disease prediction. 128 13

Type I Insulin-Dependent Diabetes Mellitus (IDDM) is an autoimmune disease characterised by the destruction of pancreatic Beta cells. There is an evidence for a contribution of genetic factors to the development of the disease and it is widely documented that HLA antigens contribute to the disease susceptibility. HLA-DR3 and HLA-DR4 associations have been firstly described in Caucasian. Recent studies at the gene level have elucidated this HLA association more precisely, pointing out the prominent role of HLA-DQ locus genes. The hypothesis has been proposed that some critical amino-acid at position 57 of DQ Beta chain and at position 52 of DQ Alpha chain both contribute to disease susceptibility. According to the functional role of HLA class II molecules, these particular residues may affect the antigen binding and T cell recognition and therefore contribute to the triggering of the pathological auto-immune response.
 ...
PMID:[Genetic susceptibility of insulin-dependent diabetes]. 129 34

Risk factors for IDD have been studied in relatives of patients, in whom the risk is far higher than in the children from the background population. Several factors have been identified as the genetic background at the HLA level (DR and DQ regions) and autoantibodies like islet cells antibodies (ICA) and insulin autoantibodies (IAA). 8,363 sera from schoolchildren (age 6-17 yr) have been tested for the presence of ICA. 150 sera (1.8%) were found positive; the prevalence rate of high ICA titres (> or = 20 uJDF) was very low: 0.2%. ICA titres remained stable over a 8 mth follow-up period. IAA have been measured on the first 2,000 sera and the prevalence rate was 1.2%. Only 3 sera were found positive for the two antibodies, one coming from a diabetic girl. The distribution of the susceptibility alleles at the DQ-HLA region was similar among the ICA-positive and ICA-negative children.
 ...
PMID:[Risk markers of insulin-dependent diabetes in the normal population]. 129 36

Genetic control of insulin dependent diabetes mellitus (IDDM) is mainly dependent on HLA genes in the major histocompatibility complex (MHC). The participation of TAP1 and TAP2 genes, located in the MHC region and coding for antigenic peptide transporters, was investigated in 116 IDDM patients and 98 normal controls using oligotyping after DNA amplification. The TAP2-B allele had a dominant protective effect, additive to that of the DR2 haplotype but antagonist to the susceptibility associated with the DR3 and/or DR4 haplotypes. The TAP2-A allele, in the homozygous state, had a predisposing effect. TAP1 allelic distribution did not differ among IDDM patients and controls. These data argue in favour of the role of peptide transporter gene in diabetogenesis.
 ...
PMID:TAP1 and TAP2 transporter genes and predisposition to insulin dependent diabetes mellitus. 130 Feb 36

1. The most common disease leading to end-stage renal disease were IDDM for Whites (36%), hypertensive NS for Blacks (26%), and CGN for Hispanics (35%) and Asians (47%). These racial differences should be taken into account in analyzing outcomes with respect to disease. 2. Differences in graft survival associated with different primary diseases were more apparent among Whites than Blacks. Race, rather than disease, was the dominant factor. 3. One-year graft survival was consistently highest for patients with IgA nephropathy (87%) and poorest for patients with SLE (78%). The difference across the spectrum of original diseases was significant (p < 0.001). 4. About 84% of White diabetics and 90% of those under age 50 had an HLA-DR3 or 4 tissue type compared with 50% of White donors (p < 0.001). The 1-year graft survival rate was 80% for DR3 or 4 IDDM patients and 74% for non-DR3/4 patients (p < 0.001). Black IDDM patients also had a significantly increased frequency of DR3 and 4 compared with Black donors (46% vs 32%, p < 0.001) and a similar trend toward higher graft survival, although the difference was not significant. 5. Of Whites transplanted with SLE, 60% had HLA-DR2 or 3 compared with 47% of donors (p < 0.001) and those with DR2 or 3 had significantly higher 1-year graft survival rates. Similar trends were noted for Blacks with SLE. 6. HLA-DR2 was present in 46 of 72 patients (64%) transplanted for Goodpasture's syndrome, compared with 28% of donors. Despite the small numbers, 1-year grafts survival was significantly better in the HLA-DR2 group (p = 0.006). 7. Significantly higher graft survival rates were observed among patients with HLA-DR1 in non-HLA-DR-associated diseases (CGN, IN, NS, or PC) but not in HLA-DR-associated diseases such as IDDM and SLE. 8. There were significant differences in recipient age and sex distributions in the major disease groups. Blacks under age 50 had significantly poorer outcomes than comparable Whites. 9. Pretransplantation health status influenced graft outcome in all disease groups. Patients with IDDM or NS were generally less healthy and correspondingly more debilitated than patients with other diseases. 10. Diabetic given a simultaneous kidney-pancreas transplant had 83% 1-year graft survival compared with 78% for those given a kidney alone (p < 0.001).
 ...
PMID:Disease effects and associations. 130 13

HLA antigens have been shown to be associated with several immunoinflammatory diseases. The mechanisms by which these antigens confer susceptibility to disease continue to be of major interest. Rapid progress has been made in the elucidation of the structure and function of class I and II MHC molecules, and several genes located within the HLA complex have been identified which are potentially involved in immunologic processes. Because of the HLA localization of the TNF-alpha and -beta genes and the biologic activities of the gene products, recent investigation has focused on a possible role of polymorphic TNF genes in the pathogenesis of HLA-associated diseases. Allelic variations have only been detected in the TNF-beta gene. No evidence has been found so far that a particular TNF-beta allele contributes significantly in the susceptibility to the diseases studied. Although it has been postulated that the TNF beta*2 allele contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a larger group of HLA-typed patients and controls is needed to provide more conclusive evidence for this hypothesis. The increasing number of genes of unknown function encoded by the class III region leaves the possibility that the observed HLA associations in some diseases may be related to the presence of these genes. In AS, the lack of association with the TNF-beta alleles furthermore supports the function of the HLA-B27 molecule in the disease and underlines the improbability that HLA-B27 is merely a marker for a closely linked susceptibility gene.
 ...
PMID:Polymorphism of the tumor necrosis factor region in relation to disease: an overview. 134 86

Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P less than 0.05) and 0% of the siblings. The CR1 gene polymorphism of the IDDM patients did not significantly differ from that of the controls. The presence of a 6.9 kb (L) CR1 gene fragment was associated with a low CR1 expression in the patients (P less than 0.05) and especially in the controls (P less than 0.001). No significant association was found between the presence or absence of the HLA risk antigens for IDDM and CR1 expression. The results confirm that erythrocyte CR1 expression is genetically determined, but the CR1 deficiency associated with IDDM seems to be an acquired rather than a genetic phenomenon.
 ...
PMID:Normal C3b receptor (CR1) genomic polymorphism in patients with insulin-dependent diabetes mellitus (IDDM): is the low erythrocyte CR1 expression an acquired phenomenon? 135 45

Population studies have suggested an increased frequency of small DNA insertions (class I alleles) 5' to the insulin gene in insulin dependent (type I) diabetes mellitus (IDDM). The present study examined this relationship within families. Forty-one families with at least one diabetic offspring were studied. Analysis of the insulin gene polymorphism was performed by digestion of DNA with Bg1I, SstI, RsaI, or PvuII and hybridisation with an insulin gene probe or polymorphic region specific probes. An increased frequency of class I alleles was found among the parents of diabetics (p = 0.02), as well as a trend towards increased frequency of parents homozygous for class I alleles and matings of two homozygous subjects. This increased homozygosity for class I alleles was present in non-diabetic sibs as well (p = 0.01). These results show that ascertainment through an offspring with IDDM selects for families with high frequencies of homozygosity for the class I allele and thus suggests that the insulin gene polymorphism is indeed providing part of the genetic predisposition to IDDM. When the major portion of genetic predisposition is provided by other genes (estimates are that HLA accounts for 30 to 70% in IDDM), identification of additional susceptibility genes becomes difficult. Even when formal linkage analysis is uninformative, our studies indicate that analysis for aggregation of specific alleles within families is a useful approach to this problem.
 ...
PMID:The aggregation of the 5' insulin gene polymorphism in insulin dependent (type I) diabetes mellitus families. 135 34

The major histocompatibility complex (MHC) contains multiple and diverse genes which may be relevant to the induction and regulation of autoimmune responses in insulin dependent diabetes mellitus (IDDM). In addition to HLA class I and II, the possible candidates include TNF, C4, and several other poorly defined polymorphic genes in the central MHC region. This study describes two approaches which take advantage of the fact that the relevant genes are carried by highly conserved ancestral haplotypes such as 8.1 (HLA-B8, TNFS, C4AQ0, C4B1, DR3, DQ2). First, three "diabetogenic" haplotypes (two Caucasoid and one Mongoloid) have been compared and it has been shown that all three share a rare allele of BAT3 as well as sharing DR3, DQ2. In 43 sequential patients with IDDM the cross product ratio for BAT3S was 4.8 (p less than 0.01) and 6.9 for HLA-B8 plus BAT3S (p less than 0.001). Second, partial or recombinant ancestral haplotypes with either HLA class I (HLA-B8) or II (HLA-DR3, DQ2) alleles were identified. Third, using haplotypic polymorphisms such as the one in BAT3, we have shown that all the patients carrying recombinants of the 8.1 ancestral haplotype share the central region adjacent to HLA-B. These findings suggest that both HLA and non-HLA genes are involved in conferring susceptibility to IDDM, and that the region between HLA-B and BAT3 contains some of the relevant genes. By contrast, similar approaches suggest that protective genes map to the HLA class II region.
 ...
PMID:Ancestral haplotypes reveal the role of the central MHC in the immunogenetics of IDDM. 135 98

The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM-associated haplotypes (n = 129) the 5.5-kb allele was more frequent than in haplotypes found only in healthy family members (n = 112) (58.1% versus 40.2%, P < 0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.
 ...
PMID:Tumour necrosis factor-beta gene RFLP alleles in Finnish IDDM haplotypes. The Childhood Diabetes in Finland (DiMe) Study Group. 136 Oct 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>