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)

Although it is now well established that insulin-dependent (type I) diabetes mellitus is closely associated with genes of the HLA-DR locus, the genetics of the disease remains an area of controversy. It is generally believed that the HLA-linked diabetes genes provide the majority of disease susceptibility to type I diabetes, however, there is some evidence for the existence of other non-HLA-linked genetic loci predisposing to this disorder. Therefore, allotypes of the Gm (immunoglobulin heavy chain) locus on chromosome 14 and of Km (immunoglobulin light chain) locus on chromosome 2 were studied in 180 caucasoid type I diabetic patients. No association between immunoglobulin allotype markers and the whole group of type I diabetes could be observed. However, a particular immunoglobulin allotype, G1m(a), and a particular Gm immunoglobulin phenotype (a-x-f+b+) showed a significant heterogeneity within the diabetics subdivided by HLA-DR type. The data of this study support the concept that (1) the genes in the HLA region provide the majority of, but not the only, genetic susceptibility to type I diabetes mellitus and (2) Gm-associated genes could interact with these susceptibility genes at least in the DR3+4 heterozygote type I diabetics. Further studies should be undertaken in order to elucidate a possible role of these factors in the humoral immune response of type I diabetics and their families.
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PMID:Immunoglobulin allotype markers and HLA DR genes in type I diabetes mellitus. 643 49

Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.
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PMID:Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes. 659 40

This report deals with the question of the susceptibility for IDD association with the recently described HLA-linked SB system. The SB system is located centromeric of HLA-DR between HLA-DR and GLO. At present five specificities of the SB system, which behave as alleles, can be recognized. A total of 40 IDD patients and 96 normal controls were characterized for HLA-A, -B, -C, -DR and SB antigens. Our results confirmed the strong positive association of IDD with HLA-DR3 and -DR4 and the negative association of IDD with HLA-DR2. The genetic analysis of the SB system and IDD, however, demonstrated no significant association between alleles of SB and susceptibility for IDD. The analysis of association between alleles of HLA-DR and SB revealed no significant linkage disequilibrium in IDD patients and a significant linkage disequilibrium between SB1 and HLA-DR3 in the controls. These results suggest that the genes associated with susceptibility for IDD are primarily coded for telomeric of SB and tightly linked with HLA-DR.
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PMID:Relation of insulin-dependent diabetes mellitus (IDD) and the HLA-linked SB system. 660 7

The Ia (immune-associated, DR) antigen is a cell surface glycoprotein which is absent on normal circulating T lymphocytes but present on activated T lymphocytes. We studied the expression of this antigen on circulating T lymphocytes from patients with untreated hyperthyroid Graves' disease. All patients (n = 33) with recent onset hyperthyroid Graves' disease studied had an increased percentage and number of circulating Ia+ T cells. Patients with non-Graves's hyperthyroidism or Graves' disease patients more than 1 yr after thyroid ablation had normal values for Ia+ T cells. Other cell surface activation antigens, recognized by monoclonal antibodies 4F2 and 5E9, were not present on circulating T cells in patients with Graves' disease. The 100% positivity for increased numbers of Ia antigen-bearing T cells in hyperthyroid Graves' disease contrasts with our finding of 70% positivity in another HLA-DR-associated disease, recent onset type I diabetes mellitus. The pathogenic significance of these cells is not known, but they seem to represent selective activation of the immune system in patients with untreated hyperthyroid Graves' disease.
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PMID:Ia+ T cells in new onset Graves' disease. 661 Jun 85

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.
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PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

HLA frequency distributions in Fiji Indians with non-insulin dependent diabetes were compared with those in control subjects with confirmed two-hour plasma glucose levels less than 7.8 mmol/L. Antigen frequencies at HLA-A and HLA-DR loci were similar in patients and controls. At HLA-B, there was a significant increase in Bw61 (Bw40.2) in diabetics, with a relative risk for this antigen of 4.8. Since a similar finding has been reported previously in South African Indians with Insulin-dependent diabetes, it is possible that wer have defined yet another genetically-distinct form of diabetes, especially prevalent in Indians. Alternatively, definition of new HLA alleles such as Bw61, a new subdivision of an established antigen, may reveal HLA associations with non-insulin dependent diabetes in European Caucasians also.
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PMID:HLA and non-insulin dependent diabetes in Fiji indians. 694 7

The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.
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PMID:HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM). 695 94

Sixty-four Japanese insulin dependent juvenile onset diabetes mellitus (JOD) were studied in relation to HLA-A, B, and DR. Significant deviations were observed. HLA-Bw54 was increased (PF = 49.2%, RR = 6.4) and HLA-B5 was decreased (PF = 7.9%, RR = 0.19). Using radioimmunoassay, two HLA-DR antigens were investigated. Hon 7 antigen, so-called MT3 (WIA4x7), which has linkage disequilibrium between HLA-BW54, is highly associated (PF = 96.9%, RR = 27.8) with JOD found in the Japanese.
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PMID:Association of B cell alloantigen with juvenile onset diabetes mellitus in the Japanese. 697 61

Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets of Langerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the H1-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by beta 2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using 125I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that greater than 95% of the cells in the beta-cell-rich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.
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PMID:Expression of major histocompatibility antigens on pancreatic islet cells. 703 53

1. In 1984, second graft survival rates were 10% lower than first grafts, but in 1992, the survival difference was reduced to 1%. Multiple grafts in 1984 were 23% lower than first grafts, but showed only a 7% difference in 1992. In 1992, 12% of kidney grafts were performed into second graft recipients and 3% into multiple graft recipients. 2. If first grafts survived one to 12 months posttransplant, the second graft survival was less than if they had survived longer than 12 months, as seen in many previous analyses. Here we showed that patients with a first graft duration of one to 12 months had a higher incidence of sensitization than patients with a first graft duration of more than 12 months. This may indicate that immunization was the cause of failure more frequently among those patients who rejected earlier than later. 3. Since 1989, the interval between first graft rejection and second graft transplantation was not a factor in second graft survival. A strong correlation was noted between high PRA and interval to regrafting. This probably reflects the increasing difficulty in finding negative-crossmatch donors as PRA increases. 4. Repeat mismatches for HLA-DR were deleterious to second grafts, although repeat mismatches for HLA-A,B were not, confirming earlier studies (1,5). HLA-A,B,DR mismatches correlated well with second and multiple transplant outcomes. 5. Patients receiving second cadaver-donor transplants had the same graft survival regardless of whether the first graft was another cadaver donor or a living-related one. On the other hand, second living-related donor transplants had a higher graft survival rate if the first graft had also been from a living-related rather than a cadaver donor (p < 0.05). This suggests that it would be advantageous if the first graft came from a living-related donor with a cadaver donor as the second graft, rather than the reverse situation. 6. Urine production on the first postoperative day was a very strong indicator of subsequent graft survival, particularly for second and multigraft patients. Failure to diurese on the first day resulted in a second graft survival of 60% at one year compared with 80% for those that diuresed on the first day. 7. Similarly, dialysis requirements were a major factor in predicting subsequent graft survival. For second graft patients who required dialysis, one-year graft survival was 63%, compared with 84% if no dialysis was needed. 8. The fraction of patients who had insulin dependent diabetes for first grafts was 27%, 15% for second grafts, and 9% for multiple grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Renal retransplantation. 754 73


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