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)

Thirty Ethiopian malnutrition-related diabetes mellitus (MRDM) patients were HLA typed and their HLA antigen frequencies were compared to those of 31 previously typed insulin-dependent diabetes mellitus (IDDM) patients and to 84 controls from the same ethnic background. In comparison to controls, a striking association between MRDM and HLA-DR3 (X2 = 15.15, p = 0.0001) was observed, whereas the frequency of HLA-DR4 was non-significantly increased (RR = 1.72). The frequency of DR2, DQw1, and DQw6 was decreased among MRDM. In comparison to IDDM that is associated with both DR3 and DR4 in this population, MRDM showed no significant differences in HLA class II antigens frequencies. Therefore, the genetic basis of susceptibility to MRDM and IDMM in Ethiopia is at least partially identical.
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PMID:HLA-DR and -DQ antigens in malnutrition-related diabetes mellitus in Ethiopians: a clue to its etiology? 262 60

HLA phenotypes and haplotypes in relation to organ-specific autoantibody responses were studied in 82 Japanese patients with Type 1 (insulin-dependent) diabetes. HLA-DRw9 antigen and HLA phenotype of DRw9/X (X:not DR4) were increased in patients with organ-specific autoantibodies other than islet cell antibody (CP less than 0.02, RR = 4.02 and p less than 0.05 RR = 2.30, respectively); whereas HLA-DR4 antigen and HLA phenotype of DR4/X (X: not DRw9) were increased in those without the autoantibodies (CP less than 0.001, RR = 3.95 and p less than 0.01, RR = 2.46, respectively). HLA haplotype of Bw61-DRw9 was increased in patients with the autoantibodies (p less than 0.005, RR = 4.94), and HLA haplotype of Bw54-DR4 was increased in those without the autoantibodies (p less than 0.001, RR = 5.52). The relative risk of HLA-DR4/DRw9 was the highest among all HLA-DR phenotypes or genotypes in patients either with or without the autoantibodies. No association was, however, found between the incidence of islet cell antibody and HLA-DR phenotypes. These findings suggest that Type 1 diabetes among Japanese is immunogenetically heterogeneous as is Type 1 diabetes among Caucasians; and the differences in HLA-association of Type 1 diabetes among ethnic groups might give a clue to understanding of a role of HLA-antigens in the development of Type 1 diabetes.
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PMID:Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese HLA antigens and organ-specific autoantibodies. 265 Nov 87

The discovery of the key role played by the immune system in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) opens up new possibilities for its early diagnosis, at the stages preceding its clinical manifestation. Analysed are the markers of genetic susceptibility to IDDM associated with some major histocompatibility complex antigens (specifically with HLA-DR 3, HLA-DR4, and HLA-DQ), of the cellular and humoral anti-islet autoimmunity, as well as the origin of the islet-cell autoantigens. The markers' significance for the diagnosis and prognosis is discussed.
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PMID:[Molecular biological aspects of the pathogenesis of diabetes mellitus]. 266 69

In spite of the potential assay problems, a relatively clear general picture concerning islet cell antibodies has emerged. They are undoubtedly the most potent indicator of risk for insulin-dependent diabetes, at least among high-risk persons (that is, first-degree relatives of insulin-dependent diabetics). Islet cell antibodies have been the focus of intense research scrutiny over the last decade, yet their etiologic role remains unclear. In patients with insulin-dependent diabetes, there is no striking relation at onset between islet cell antibodies and determinants such as age and HLA type. Certain characteristics, however, may be related to islet cell autoimmunity in a more complex way. There appears to be some racial difference in onset-related islet cell antibody prevalence and other autoimmunity. The observation that autoimmune abnormalities are more frequent among women and among diabetics leads to the question of whether there is an interaction of sex and autoimmune diabetes. There may be a group of early-onset patients, distinguished by persistent islet cell antibodies or coexistent autoimmune phenomena, who are predominantly female. At present, there is only limited evidence for this in the literature: Bottazzo et al. found that juvenile diabetics with persistent islet cell antibodies were more often female. Female diabetics have been shown to have an increased prevalence of thyroid autoantibodies compared with male diabetics. Several observations of differences based on sex have emerged from recent studies of insulin-dependent diabetes: 1) the HLA-DR4 antigen is more frequent among female diabetic patients; 2) male HLA-identical siblings of diabetics have a lowered insulin response to glucose administered intravenously; 3) in areas of low insulin-dependent diabetes incidence, the patterns of onset by age differ markedly between the sexes. These sex-specific differences may help to clarify the relation between islet cell autoimmunity and sex. Among nondiabetic persons, those having the highest genetic "risk" for disease appear to have an increased prevalence of islet cell antibodies. There is also some indication that HLA-DR3 may be associated with islet cell autoimmunity. Other related diseases, notably gestational diabetes, non-insulin-dependent diabetes, and certain autoimmune endocrinopathies, are associated with an increased prevalence of islet cell antibodies. An increase in islet cell antibody prevalence occurs in certain viral infections, particularly mumps and congenital rubella. Islet cell antibodies have been noted in the sera of subjects many years before the onset of insulin-dependent diabetes, as well as in normoglycemic relatives.
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PMID:Epidemiology of islet cell antibodies. 268 May 55

The human major histocompatibility complex includes approximately 14 class II HLA genes within the HLA-D region, most of which exist in multiple allelic forms. One of these genes, the DQ3.2 beta gene, accounts for the well-documented association of HLA-DR4 with insulin-dependent diabetes mellitus and is the single allele most highly correlated with this disease. We analyzed the amino acid substitutions that lead to the structural differences distinguishing DQ3.2 beta from its nondiabetogenic, but closely related allele, DQ3.1 beta. Site-directed mutagenesis of the DQ3.2 beta gene was used to convert key nucleotides into DQ3.1 beta codons. Subsequent expression studies of these mutated DQ3.2 beta clones using retroviral vectors defined amino acid 45 as critical for generating serologic epitopes characterizing the DQw3.1 beta and DQw3.2 beta molecules.
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PMID:Mutational analysis of the HLA-DQ3.2 insulin-dependent diabetes mellitus susceptibility gene. 278 80

HLA-DR4 is associated with insulin-dependent diabetes mellitus (IDDM) in many populations. Many recent studies suggest that the DR4 effect is really due to DQ3.2, an allele of the nearby DQB1 locus. We used T cell clones, MAb, and allele-specific oligonucleotides to test IDDM and control subjects for DR4 subtypes (Dw4, Dw10, Dw13, and Dw14) and for DR4-associated DQB1 alleles (DQ3.1 and DQ3.2). We find that (a) IDDM is approximately equally associated with alleles of the DRB1 locus (Dw4 and Dw10, combined relative risk, RR = 6.4) and the DQB1 locus (DQ3.2, RR = 5.9); and (b) there is significant interaction, in a statistical sense, between these DR and DQ alleles in IDDM. The only IDDM-associated DR4 haplotypes were those carrying the IDDM-associated alleles at both loci (RR = 12.1); haplotypes with Dw4 or 10 but not DQ3.2, or vice versa, had a RR less than 1. Alternative explanations include: (a) that susceptibility requires specific allelic products of both DR and DQ loci; (b) that the combination of certain DR and DQ alleles marks haplotypes with the true susceptibility allele at a third locus; or (c) that Dw4 and 10 mark haplotypes with an allele at another locus that interacts with DQ3.2. As discussed, this third locus is unlikely to be DQA1 (DQ alpha). The data thus are not easily reconciled with an exclusive effect of HLA-DQ. This information increases our ability to predict IDDM by genetic typing: in the population studied, heterozygotes DR3/[DQ3.2, Dw4] or DR3/[DQ3.2, Dw10] had a relative risk of 38.0 and an absolute risk of 1 in 15.
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PMID:A diabetes-susceptible HLA haplotype is best defined by a combination of HLA-DR and -DQ alleles. 278 33

The patterns of migration and the genetic disorders occurring among North American Mennonites are reviewed, and inherited conditions recently recognized in a religious and genetic isolate, the Old Colony (Chortitza) Mennonites, are described. Old Colony Mennonites are of Dutch/German origin and descend from approximately 400 founding families who settled in the Old Colony, Chortitza (the Ukraine, USSR) in the late 1700s, and then migrated to Canada and Central and South America in the past century. We investigated over 6 generations of a Canadian Old Colony kindred in which there was extensive intermarriage, and in whom 28 individuals developed diabetes mellitus. Insulin-dependent diabetes mellitus (IDDM) occurred in 14 affected individuals in 10 closely related sibships; the 11 living IDDM patients were all concordant for the immunogenetic marker HLA-DR4. Fourteen close relatives had other disorders of carbohydrate metabolism, including gestational diabetes and non-insulin-dependent diabetes mellitus. Other close relatives had autoimmune diseases, including rheumatoid arthritis, hyper- and hypothyroidism, multiple sclerosis, and red cell aplasia. Other inherited diseases, including Alport syndrome, congenital defects, and inborn errors of metabolism were also found in the kindred. In the almost exclusively (99%) Old Colony Mennonite public health district in which the kindred was ascertained, there were multiple cases of Tourette syndrome, of malformations (including congenital heart defects and cleft lip +/- palate), and familial clusters of inborn errors of metabolism. We report this Old Colony (Chortitza) Mennonite isolate because 1) there are large familial aggregations of tissue-specific autoimmune diseases, malformations, inborn errors of metabolism, and of some other conditions whose genetic basis is still unknown; 2) there are multiple cases of rare genetic conditions, 3) we have established a computerized genealogic data base on over 1,000 kindred members as well as a cryopreserved lymphocyte/DNA bank on over 100 closely related individuals with various genetic conditions; and 4) this religious isolate, which extends across North, Central, and South America, offers an excellent opportunity for studying the epidemiology and molecular genetics of both common and rare inherited diseases.
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PMID:Inherited diseases in North American Mennonites: focus on Old Colony (Chortitza) Mennonites. 278 28

DNA from 164 Caucasian type I (insulin-dependent) diabetic patients and 200 Caucasian nondiabetic control blood donors were analyzed by the polymerase chain reaction technique for HLA-DR4 and the associated Dw and DQB subtypes of DR4. The DQw8 subtype of HLA-DR4 was associated with type I diabetes in all DR4 subgroups (DR4/3 and DR4/non-3). Dw subtypes of DR4 other than DW10 did not confer additional association with type I diabetes. Thus, the DQ region appears to provide the primary major histocompatibility association with type I diabetes in most DR4 patients.
Diabetes 1989 Jul
PMID:Primary association of HLA-DQw8 with type I diabetes in DR4 patients. 278 21

The predominant genetic elements contributing to HLA-associated disease susceptibility have been localized within the HLA-D, or class II, region of the major histocompatibility complex for a large number of autoimmune diseases. Two likely candidate susceptibility genes in this region have been identified: the DQ beta 3.2 gene is the single allele most highly associated with type I diabetes (IDDM) and accounts for the HLA-DR4 association with that disease. DNA sequence analysis and mutagenesis studies implicate a small set of key residues within the DQ3.2 molecule as critical polymorphic residues likely contributing to disease-associated immune mechanisms. Different class II genes, Dw4 and Dw14, specific alleles at the DR beta locus, account for the HLA-DR4 association with rheumatoid arthritis (RA). A single cluster of polymorphic residues within the DR beta molecule may be sufficient to account for nearly all of the structural and genetic contributions of the HLA complex to the pathogenesis of RA.
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PMID:Determinants of genetic susceptibility in HLA-associated autoimmune disease. 279 47

It is well established that there is genetic heterogeneity between a human lymphocyte antigen (HLA)-DR3-associated allele and an HLA-DR4-associated allele in insulin-dependent diabetes mellitus (IDDM). Equally well established are the association of DR3 with Graves' disease and other autoimmune disorders in nondiabetics and the increased prevalence of autoimmune thyroid disease in IDDM. Perhaps in large part because of these facts, it has been postulated that there are two major forms of classical IDDM--one form characterized by coexistent autoimmune disease, such as autoimmune thyroid disease which is associated with DR3, and another form not associated with additional autoimmune disorders, which is associated with DR4. Several studies have repudiated the idea of specific clinical findings in IDDM being associated exclusively with DR4. However, the DR3-thyroid association in IDDM has not been investigated carefully. Therefore, in order to study this putative association, we divided a group of diabetic children into overlapping subgroups based on thyroid enlargement, antithyroid microsomal antibodies, acquired hypothyroidism, and no evidence of thyroid disease. The distributions of HLA-DR3 and -DR4 among these subgroups did not differ from each other; nor did the distribution of the HLA alleles differ from those of randomly selected IDDM individuals. These results suggest that thyroid autoimmunity in IDDM is part of the IDDM "syndrome" and is associated with DR3 and DR4 to the same extent that IDDM without thyroid disease is associated with these two antigens. Thus, although genetic studies are consistent with the heterogeneity between DR3 and DR4 in IDDM, there is no HLA-thyroid disease association to support this heterogeneity.
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PMID:Autoimmune thyroid phenomena are not evidence for human lymphocyte antigen-genetic heterogeneity in insulin-dependent diabetes. 280 76


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