Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It now appears unequivocal that three markers exist in a linkage group in chromosome 6 of man: HLA-A, HLA-B and PGM3 (Fig. 1.) Tentatively, two other HLA loci and one Ir gene have been mapped close to HLA-B. The probable map order is HLA-A - HLA-C - HLA-B - HLA-D - Ir. The biological functions of these loci are unknown. However, HLA-A, B and C are important in allograft rejection. Other closely linked loci (HDR, CML) appear to be important in the first events of the allograft rejection (first set) and in generation of killer cells. HLA-D might be important in cellular recognition and graft-versus-host reactions (matching at HLA-D decreases the incidence and severity of graft-versus-host disease), and the Ir genes in the defense against infections. HLA-B and HLA-D loci are important markers in studies of disease susceptibility. HLA-B locus antigens HLA-B27 and HLA-B8 are frequently associated with arthritic or autoimmune disorders. HLA-D determinants have been found in association with multiple sclerosis and C2 deficiency (HLA-DW2); juvenile diabetes and Addison's disease (HLA-DW3) and adult type of rheumatoid arthritis (HLA-DW4).
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PMID:Immunogenetic aspects of allotransplantation. 13 74

HLA typing was performed in 90 unrelated patients with chronic alcohol-associated pancreatitis. Compared with 523 healthy controls, an increased frequency was found for the HLA-B series antigen, B40 (Pless than 0.00041, corrected P less than 0.011). The increase was slightly more pronounced in patients without pancreatic calcifications than in those with calcifications. Factors such as alcohol consumption, age of disease onset and the presence of diabetes did not affect antigen frequency distribution.
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PMID:HLA antigens in chronic alcoholic pancreatitis. 44 66

To study the association of histocompatibility (HLA) genes in black persons with juvenile-onset diabetes, we determined HLA-A, HLA-B, HLA-C and HLA-DR specificities in 40 black Americans with this disease and in 67 unaffected black Americans. Marked increases in the frequencies of HLA-DRw3 and HLA-DRw4 were found in the patients as compared with the unaffected persons: DRw3 was found in 72.5 per cent of patients versus 29.9 per cent of unaffected persons and DRw4 in 72.5 per cent versus 25.4 per cent (corrected P values each less than 0.0007). DRw2 was not found in any of the patients but was present in 26.9 per cent of unaffected persons (P corrected less than 0.035). There is thus a negative correlation between this specificity and juvenile-onset diabetes. By contrast, no meaningful differences were found in the frequencies of A, B, or C locus antigens. Studies in white persons with juvenile-onset diabetes have suggested that the reported HLA-B associations are due to HLA-D region specificities, and our results also support the premise that D region specificities are the primary associations with juvenile-onset diabetes.
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PMID:HLA-DR specificities among black Americans with juvenile-onset diabetes. 48 12

We examined the graft survival of 12,883 first unrelated kidney grafts from nonliving donors, transplanted between 1 January 1971 and 31 December 1987 within 52 renal transplantation centers participating in the Eurotransplant organization. The 5-year graft survival increased from 38.8% for the period 1971-1975 to 66.0% for the period 1981-1987 for patients treated with cyclosporine, whereas the half-life increased by only 2 years, from 9.7 years to 11.6 years over the same period, based on grafts functioning at 1 year posttransplantation. Results per HLA locus showed considerable improvements within mismatch groups over the entire period. Large differences between mismatch groups for the early years were observed, but within the cyclosporine era only HLA-B showed a statistically significant difference in half-lives (13.2 versus 9.0 years, for 0 and 2 mismatches respectively, P = 0.013). When other prognostic factors were taken into account, it was revealed by means of an exponential model that number of HLA-B mismatches, donor and recipient age and sex, and recipient diagnosis of diabetes had significant effects on the long-term outcome of the grafts. Depending on the combination of these parameters, estimates of half-life varied from 4.9 to 14.5 years. These results show that matching for HLA-B is still of benefit in the longer term and that other prognostic factors play an important role in predicting the late outcome of renal allografts.
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PMID:Factors contributing to long-term kidney graft survival in Eurotransplant. 163 24

Tumour necrosis factors alpha and beta (TNF-alpha and TNF-beta) and gamma interferon (IFN-gamma) were measured by ELISA in the supernatants of phytohaemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMNC) from 98 individuals (60 controls and 38 patients with insulin-dependent diabetes mellitus [IDDM]). The PBMNC were incubated with varying concentrations of PHA (0, 1, 5, and 10 micrograms/ml) for 72 h. In our population study we observed a correlation between the levels of secretion of TNF-alpha and IFN-gamma but not TNF-beta. The complete data set was analysed by non-parametric tests, and no associations with HLA phenotypes existed. Reduced levels of TNF-beta, but not TNF-alpha or IFN-gamma, secretion were found in IDDM patients stimulated with 1 and 5 micrograms/ml of PHA (P = 0.001 and 0.02 respectively). None of the lymphokine secretion levels at any PHA concentration correlated with particular HLA phenotypes. Analysis of the natural log-transformed data indicated that only for the TNF-beta levels (at 5 micrograms/ml PHA) could subjects be divided into high and low secretors, which also did not correlate with a particular HLA-B or -DR antigen.
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PMID:The effect of HLA and insulin-dependent diabetes mellitus on the secretion levels of tumour necrosis factors alpha and beta and gamma interferon. 212 64

A log-linear model was used to analyze three-way interactions between IDDM and pairs of genetic markers. To do this, a special sample dataset was selected by taking one affected and one unaffected child from each family. Some three-way interactions were found for associations between insulin-dependent diabetes mellitus (IDDM), HLA-DR, and DQ restriction enzyme fragment length polymorphism (RFLP) patterns. No three-way interaction was found for IDDM, HLA-DR, and Gm or Km. An extended sibpair analysis was applied to the HLA-B,DR loci and to the Gm, Km, and insulin gene polymorphisms. The well-known result for IDDM and HLA was reproduced. For Gm, Km, and the insulin gene no cosegregation with IDDM could be found.
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PMID:Association and sibpair analysis for the HLA, Gm, Km, and insulin polymorphisms in multiplex IDDM families. 256 52

Diabetes mellitus is the second most prevalent chronic disease in children in the U.S. It is associated with severe manifestations which include blindness and circulation deficiencies as well as markedly increased risk of death. The etiology of diabetes mellitus remains a mystery although both genetic and environmental factors have been implicated. The geneticist is confronted with a number of obstacles in his attempts to unravel this problem, including differences in the definition of affected individuals. This matter was certainly clarified by the separation of noninsulin-dependent diabetes (NIDDM) and insulin-dependent diabetes mellitus (IDDM) into two separate disease entities. Twin studies, however, show that IDDM cannot be entirely due to genetic causes as concordance is no more than about 50%. Although the disease is then clearly not inherited per se, the "susceptibility" to diabetes seems almost surely inherited and, provided this susceptibility, the disease can be brought on by environmental factors. Until the underlying mechanism causing IDDM is completely ascertained, we have to rely on genetic markers to approach the study of the inheritance thereof. Since, in the early 1970s, research by Nerup's and Cudworth's groups revealed associations between the HLA-B locus and IDDM, the HLA markers are considered the classical genetic markers for IDDM susceptibility. In this paper, we review the nature of the genetic susceptibility to IDDM and the possible environmental factors which can bring on the disease.
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PMID:Immunogenetics of insulin-dependent diabetes mellitus in humans. 257 May 96

Type 1 (insulin-dependent) diabetes mellitus, like some other autoimmune diseases, is linked to certain alleles coded by genes in the HLA-D region. Sequence analysis of DQ beta chains indicates that aspartic acid at codon 57 confers resistance to the development of Type 1 diabetes. However, a full explanation for the HLA-association of Type 1 diabetes, particularly the increased susceptibility of DR3/4 heterozygotes is still awaited. The localisation of tumour necrosis factor genes on the short arm of chromosome 6 between HLA-B and the complement genes (Class III) prompted us to investigate a possible polymorphism of TNF-alpha at the genomic level in relation to Type 1 diabetes susceptibility. A dialleleic TNF-alpha restriction fragment length polymorphism was found with Ncol and its segregation with HLA-haplotypes analysed in diabetic families. We describe here a strong linkage of TNF-alpha alleles with certain DR haplotypes. For example, the common extended haplotype HLA A1-B8-DR3 was almost exclusively associated with the 5.5 kb TNF-alpha allele whereas Bw62-DR4 with the 10.5 kb allele. Thus both alleles segregate to diabetic patients. DR matched haplotypes of affected family members differed significantly from those of the non-affected at the TNF alpha locus. All affected sibling pairs in 11 multiplex affected families were identical for TNF-alpha alleles, even if they were only haploidentical for HLA-B-DR haplotypes. In addition, heterozygosity for the TNF-alpha alleles was significantly more frequent in the patients. This tight linkage of TNF-alpha alleles with some extended haplotypes could help to explain the HLA-association of Type 1 diabetes as well as some other autoimmune diseases.
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PMID:TNF-alpha gene polymorphisms in type 1 (insulin-dependent) diabetes mellitus. 257 98

The aim of this study was to investigate a possible reenhancement of islet cell autoimmunity in type I (insulin-dependent) diabetic patients who received HLA-mismatched pancreas transplants from cadaveric donors and who underwent generalized immunosuppression. Circulating islet cell antibodies (ICA) and complement-fixing ICAs (CF-ICAs) have been tested at 1, 2, 3, 6, and 12 mo and at least once a year posttransplantation in 23 recipients of 25 transplants (22 simultaneous with kidney, 2 retransplants, 1 isolated; 23 segmental neoprene injected, 2 whole with enteric drainage). Patients were aged 35.3 +/- 1.9 yr with a duration of diabetes of 20.6 +/- 1.1 yr. Immunosuppression consisted of double or triple association of azathioprine, cyclosporin, and prednisone with or without temporary antilymphocyte globulins. The number of HLA-A and HLA-B compatibilities was none in 8 patients, one in 12 patients, two in 4 patients, and three in 1 patient. The mean follow-up was 4.0 +/- 0.4 yr/patient (range 0.4-7.2). ICAs were positive pretransplantation in 2 of 25 patients and reappeared 1-42 mo posttransplantation in another 7. In 6 patients, CF-ICAs were also positive. In 7 of 9 ICA+ patients the pancreas transplant failed; in 1 patient this occurred 4 mo before ICA reappearance, and in 6 patients it occurred 2-35 mo after the first detection of ICAs. Pancreas-transplant failure was significantly associated with the positivity for ICAs (P less than .05) and particularly for CF-ICAs (P less than .005). ICA positivity was transitory in 4 patients (2-27 mo) and persistent in the remaining 5 (up to 61 mo).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Jan
PMID:Islet cell autoimmunity in type I diabetic patients after HLA-mismatched pancreas transplantation. 264 61

The study of HLA histocompatibility antigens and insulin-dependent diabetes mellitus (IDDM) in non-White populations may provide a unique opportunity to more accurately define the diabetes susceptibility gene(s) located within the HLA region. To determine whether HLA haplotypes differ between ethnic groups, we compared 105 HLA haplotypes from 55 Mexican-American IDDM patients with 272 haplotypes from 136 IDDM patients of non-Hispanic White descent. The accurate determination of genotypes and haplotypes requires the study of family units. Therefore, all diabetic patients in this study were from studies of families having one or more siblings with IDDM. In the Mexican-American group, HLA-DR3 and -DR4 were the most common HLA-DR alleles and were present in comparable frequencies in the non-Hispanic White group (HLA-DR3, 27% of Mexican-American and 29% of non-Hispanic White haplotypes; DR4, 46% of Mexican-American and 43% of non-Hispanic White haplotypes). However, the HLA-B/DR-containing haplotypes and haplotype frequencies differed between the two groups. Several common haplotypes (B8/DR3, B15/DR4) in the non-Hispanic White group occurred less frequently in the Mexican-American group. In contrast, uncommon haplotypes in the non-Hispanic White group comprised nearly 50% of the DR4-containing haplotypes (B35/DR4, B40/DR4, B44/DR4) in the Mexican-American group. Although both DR3- and DR4-haplotype frequencies differed significantly between the two groups, the relative frequency of DR3- but not DR4-containing haplotypes was similar in both ethnic groups. This adds to the evidence suggesting that different susceptibilities are provided by the haplotypes carrying the DR3 and DR4 alleles.
Diabetes Care
PMID:Different HLA haplotypes in Mexican Americans with IDDM. 275 54


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