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)

Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were > 2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or-DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM.
 ...
PMID:Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. 128 Feb 39

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

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

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

Major determinants of susceptibility to Type 1 (insulin-dependent) diabetes (IDDM) have been mapped to the HLA complex, near to or identical with genes encoding class II molecules. The association of IDDM with HLA-DR3 and/or DR4 antigens and the highest risk for DR3/4 heterozygotes suggest a synergistic effect of the two haplotypes. The characterization at the molecular level of the class II region has provided evidence that DQ rather than DR determinants may primarily influence the disease. In caucasians the susceptibility strongly correlates with the absence of aspartic acid at position 57 on the DQ beta chain and/or the presence of arginine at position 52 on the DQ alpha chain. The formation of a putative DQ susceptibility molecule (DQ alpha Arg52+, DQ beta Asp57-) accounts best for the disease associations when trans-complementation between alpha and beta chains encoded by different haplotypes is postulated to explain the excess of heterozygotes. Observations in other populations and in animal models indicate, however, that other residues on DQ alpha and beta chains, other class II (DR beta) molecules and non-HLA linked genes also contribute to the susceptibility. The mechanism(s) by which susceptibility determinants influence IDDM is not known. It is probably in relation with the role of class II molecules in the antigen presentation to T lymphocytes.
 ...
PMID:[The role of the HLA system in the genetics of Type I diabetes mellitus]. 145 12

Insulin-dependent diabetes mellitus (IDDM) in Caucasians is strongly associated with HLA-DR3-DQ2 and DR4-DQ8. In order to investigate the HLA class II associations with IDDM in Algerians, we have used polymerase chain reaction (PCR) and sequence specific oligonucleotide analysis (SSO) to identify DQA1, DQB1, and DRB1 alleles, haplotypes and genotypes in 50 unrelated IDDM patients and 46 controls from a homogeneous population in Western Algeria. Both DRB1*0301-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) haplotypes were found at increased frequencies among the patients compared to controls (45% vs. 13%, RR = 5.5, Pc < 10(-5) and 37% vs. 4%, RR = 12.9, Pc < 10(-4), respectively). Among the latter, in contrast to other Caucasian populations, only DRB1*0405-DQA1*0301-DQB1*0302 was significantly increased in the Algerian patients (25% vs. 1% in controls, RR = 30.3, Pc < 10(-3). Accordingly, the highest risk of disease was observed in DRB1*0301-DQA1*0501-DQB1*0201/DRB1*0405-DQA1+ ++*0301-DQB1*0302 heterozygotes (34% in patients vs. 0% in controls; RR = 49; Pc < 10(-3). This observation and its comparison with DR-DQ haplotypes in other ethnic groups suggest that the DRB1*0405 allele which encodes an Asp57-negative beta chain may contribute to IDDM susceptibility in a similar way as Asp57-negative DQ beta chains.
 ...
PMID:The HLA-DRB1*0405 haplotype is most strongly associated with IDDM in Algerians. 147 90

MHC associations with IDDM in a Chinese population were studied to investigate genetic susceptibility to the disorder. The frequency of HLA-DR3 was significantly higher in the diabetic patients (19/49 [38.7%] vs. control subjects, 11/105 [10.5%], Pc less than 1.3 x 10(-3), RR = 5.3 [CI 2.3-12.1]), whereas DR4 was not (11/49 [22.4%] vs. 28/105 [26.7%], NS). The frequency of DR3/4 heterozygosity was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 0/105 [0%], P = 1.7 x 10(-3), RR = 31.5 [CI 3.8-263.6]). The frequency of DR3/9 heterozygosity also was higher in the diabetic patients (6/49 [12.2%] vs. control subjects, 2/105 [1.9%], P = 0.03, RR = 6.2 [CI 3.0-12.7]). No significant associations were noted between DQB1 alleles and IDDM. Among DR4-positive subjects, the frequency of DQB1 allele DQB1*0302 was higher in the diabetic patients (10/11 [90.0%] vs. control subjects, 12/24 [50%], Pc less than 0.05, RR = 7.0 [CI 1.3-38.0]), and the frequency of DQB1*0401 was significantly lower in the diabetic patients (2/11 [18.2%] vs. control subjects, 16/24 [66.7%], Pc = 0.04, RR = 0.1 [CI 0.02-0.46]). No DR4 subtype was associated significantly with IDDM. The frequency of DQA1*0501, a DQA1 allele, was higher in diabetic patients (22/41 [53.7%] vs. control subjects, 20/95 [21.1%], Pc less than 3 x 10(-3), RR = 4.3 [CI 2.0-9.3]). The frequency of DQA1*0301, which has been associated consistently with IDDM in other ethnic groups, was not significantly higher in the diabetic patients in this study (27/41 [65.9%] vs. control subjects, 53/95 [55.8%], NS).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Susceptibility to IDDM in a Chinese population. Role of HLA class II alleles. 162 65

Particular HLA-DQ beta chain alleles were reported as immunogenetic markers of type I diabetes mellitus with young onset of the disease. In a homogeneous German population, we studied HLA-DR specificities and HLA-DQ beta chain alleles in young-onset (less than 21 years of age; n = 185) and adult-onset (greater than 40 years of age; n = 48) insulin-dependent diabetics. In both cohorts of type I diabetics, the HLA-DR3 and -DR4 specificities were significantly increased. The presence of an HLA haplotype with an amino acid other than aspartic acid at position 57 of the DQ beta chain was significantly associated with type I diabetes in both cohorts (etiologic fraction: 93% and 73%). We conclude that the presence of DNA sequences coding for an amino acid other than aspartic acid at the 57th position of the DQ beta chain provides a molecular risk marker for type I diabetes of both and adult onset.
 ...
PMID:Prevalence of HLA-DQ beta chain non-Asp alleles in type I (insulin-dependent) diabetics with young and older ages of onset. 179 91

An analysis of the HLA-types of 351 children in whom a diagnosis of insulin dependent diabetes mellitus (IDDM) had been made between 1960 and 1990 revealed that although the frequencies of HLA-DR3, -DR4, -DR3/4, -B8 and -Bw62 were increased there was, depending on the year of diagnosis, a marked fluctuation in the frequencies of these HLA-antigens and in the frequency with which -B8 was associated with -DR3 and -Bw62 with -DR4 suggesting heterogeneity/variation in agents initiating/triggering IDDM.
 ...
PMID:Frequencies of HLA-DR3, -DR4, -B8 and -Bw62 in diabetic children diagnosed between 1960 and 1990. 180 81


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