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)

IgG antibody titres to Coxsackie B1-B6 were measured in 113 insulin-dependent diabetes mellitus (IDDM) patients whose mean age was 12.2 years and mean duration of IDDM was 4.6 years, and in 87 normal sibling controls whose mean age was 13.8 years. Compared with their normal siblings, the diabetics had a significantly increased frequency of high response (titre greater than or equal to 320) to Coxsackie B2 (8% versus 1%, p = 0.028), to Coxsackie B4 (15% versus 1%, p = 0.0006), and to Coxsackie B viruses in general (25% versus 5%, p = 0.0001). The frequencies of HLA-DR and immunoglobulin (GM, KM) antigens did not differ between diabetics with and without a high response to Coxsackie B2, B4, or B viruses in general. We conclude that there is an association between IDDM and IgG response to Coxsackie B2, B4, and B viruses in general, a finding which is consistent with the interpretation that infection with Coxsackie B viruses, especially B4, may initiate the development of IDDM in a portion of individuals who have HLA-DR region susceptibility genes.
Diabetes Res 1987 Dec
PMID:The relationship between Coxsackie-B-virus-specific IgG responses and genetic factors (HLA-DR, GM, KM) in insulin-dependent diabetes mellitus. 283 33

Alterations in T-lymphocyte subsets have been connected to the autoimmune pathogenesis of Type 1 (insulin-dependent) diabetes. In this study peripheral blood lymphocytes were analysed by flow cytometry using OKT3, OKT4, OKT8, anti-HLA-DR, anti-IL-2 receptor and anti-membrane immunoglobulin antibodies in newly diagnosed Type 1 diabetic children, their healthy siblings and healthy control children. The results were compared to the occurrence of serologically verified recent virus infections, some of which can induce lymphocyte subset alterations and have also been connected with the onset of diabetes. In most diabetic patients the amounts of OKT3, OKT4, OKT8 and membrane-Ig-positive cells were within the normal range. Exceptional helper/inducer and suppressor/cytotoxic T cell profiles were observed in a few patients, most of whom had serologically verified recent Epstein-Barr, rubella, mumps or Coxsackie B virus infection. In addition, increased numbers of activated IL-2 receptor-positive cells were observed in the patient group. These results suggest that significant lymphocyte subset alterations are not characteristic of Type 1 diabetes but can occasionally be induced by recent virus infections in newly diagnosed patients. However, the slight increase in activated lymphocytes could reflect the activation of cellular immune systems to the autoantigens in the pancreas.
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PMID:Flow-cytometric analysis of lymphocyte subsets in relation to virus infections at the onset of type 1 (insulin-dependent) diabetes. 284 9

Insulin autoantibodies (IAA) were studied in newly diagnosed insulin-dependent diabetics before the start of insulin treatment and in unaffected identical twins of insulin-dependent diabetics. In 15 of the 40 (38%) diabetics and 27 of the 58 (47%) twins IAA levels exceeded those of 100 controls. Frequency of IAA in unaffected twins was not related to duration of diabetes in their affected twin. In 11 unaffected twins, IAA levels differed in two samples taken 1-12 years apart; IAA were detected at least once in all twins and in one on both occasions. IAA in the twins were not related to the presence of islet-cell antibodies or to HLA-DR 3 or 4. As the unaffected twins of longstanding diabetics are unlikely to develop diabetes, these observations suggest that IAA do not always presage diabetes and are probably not a consequence of the disease; they may reflect an inherited autoimmune tendency to diabetes.
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PMID:Value of insulin autoantibodies as serum markers for insulin-dependent diabetes mellitus. 285 52

A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ beta-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ beta-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA-DR3/4 controls but in 0 of 13 DR-identical IDDM patients. All IDDM patients (13 of 13) had BamHI fragments of 12 and 4 kb, detected in 9 of 17 controls (P less than 0.02). The simple restriction fragment length polymorphism pattern of the IVS 1 probe was exploited by comparing 113 IDDM patients with 177 healthy controls to show increased prevalences in IDDM of the 12-kb (P less than 0.0001) and 4-kb (P less than 0.0001) fragments. In IDDM patients younger than 20 yr at onset, 98% were 12- and/or 4-kb positive, compared with 63% of controls (P less than 0.0001), giving a relative risk of 91.8 for individuals with both fragments. The 12-kb fragment was linked to HLA-DR4, and the 4-kb fragment to HLA-DR3. Both serologic markers were split and a non-DR3/non-DR4 IDDM patient was 4-kb positive. HLA-DQ seems therefore closer, than HLA-DR, to an IDDM susceptibility gene.
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PMID:Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ. 288 47

Thirty-six consecutive paediatric patients (0-16 years old) with recently contracted juvenile diabetes (IDDM) during 1982-84 were included in the study. Sera were assayed for recent or current Coxsackie B virus (CBV) infection using a specific and sensitive IgM RIA. Eighteen patients (50%) had IgM against CBV 1-5. The patients were also assayed for restriction fragment length polymorphism (RFLP) patterns with DNA probes coding for HLA-DR and DQ beta chains. The CBV-positive patients (n = 18) had either RFLP patterns associated with HLA-DR 3 or 4 or HLA-DQ patterns III or IV beta. Two of the CBV negative patients had neither HLA-DR 3 nor DR 4 and four of them had neither DQ patterns III nor IV. Eleven out of 18 CBV-positive patients had HLA-DQ III and DR 3 (61%) versus 5 out of 18 (28%) of the CBV-negative patients. All 11 patients with serology positive for CBV 2, 3, and 5 had HLA-DR 4 and DQ IV patterns. This was significantly (P less than 0.01) different from all five CBV 4-positive patients, who in contrast all had HLA-DR 3 or HLA-DQ III patterns. CBV 1-positive patients (n = 2) all had HLA-DR 3, 4, and HLA-DQ III, IV patterns. Thus CBV 4 seems to be significantly associated with a different host genetic constitution from at any rate CBV 2, 3, and 5, and possibly CBV 1.
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PMID:Matching of host genotype and serotypes of Coxsackie B virus in the development of juvenile diabetes. 288 88

A genetic analysis of diabetic and non-diabetic Punjabi Sikhs (n = 164) was made for markers of non-insulin-dependent diabetes mellitus using insulin receptor, insulin, and HLA-D alpha chain gene probes. Additionally British Caucasoids (n = 163) were studied using the insulin receptor probe. Insulin receptor gene restriction fragment length polymorphisms were defined using Southern blot techniques and the restriction enzyme Bgl II and BAm Hl. In Punjabi Sikhs and British Caucasoids neither of the restriction fragment length polymorphisms distinguished non-insulin-dependent diabetes mellitus subjects from controls. In the Sikhs no association with non-insulin-dependent diabetes mellitus was seen with the hypervariable region of the insulin gene or with HLA-DR/DQ/DX alpha chain restriction fragment length polymorphisms. We therefore conclude that despite the high prevalence of non-insulin-dependent diabetes mellitus in Asians we were unable to find any genetic markers for this disease using the available cloned gene probes.
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PMID:A genetic analysis of type 2 (non-insulin-dependent) diabetes mellitus in Punjabi Sikhs and British Caucasoid patients. 289 7

Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of HLA products encoded by the DR2 haplotypes of IDDM patients. The results show the following: (i) HLA-DQ molecules of HLA-DRw15-positive IDDM patients are different from those of HLA-DRw15-positive controls, suggesting that the HLA-DQ gene of DRw15 haplotypes is involved in a protective effect. (ii) HLA-DR and -DQ products of DRw16-positive IDDM are functionally indistinguishable from those of HLA-DRw16-positive controls. Furthermore, our data provide evidence that the residue at position 57 on the DQ beta chain could play a crucial biological role in antigen presentation to T cells as far as the DRw16 haplotype is concerned. This observation fits with the recent observation of correlation between DQ beta allelic polymorphism at position 57 and both susceptibility and resistance to IDDM.
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PMID:HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes. 290 Oct 99

Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for BglII restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor beta-chain (TLR beta)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P less than .02) and 2.42 (P less than .01), respectively. Hybridization of digested DNA with the TLR beta probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P less than .05) higher than that in normal subjects (64%). When TLR beta-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P less than .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLR beta-region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLR beta loci, as has been demonstrated in Caucasians.
Diabetes 1988 Dec
PMID:Association of HLA-DR phenotypes and T-lymphocyte-receptor beta-chain-region RFLP with IDDM in Japanese. 290 35

In order to ascertain whether the immunoglobulin heavy chain genes are important in the aetiology of Type 1 diabetes, we have used restriction fragment length polymorphism (RFLP) analysis of genomic DNA to study 148 Caucasoid subjects with Type 1 diabetes and 146 normal Caucasoid subjects. A DNA probe homologous to the switch regions for the IgM (S mu) and IgA1 (S alpha 1) genes when used in conjunction with the restriction endonuclease Sst I detects RFLPs at both these loci. There were no significant differences in phenotype or gene frequencies for the alleles of S mu or S alpha 1 in the patients when compared with control subjects; nor were there significant associations of S mu or S alpha 1 with HLA-DR type or gender.
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PMID:Immunoglobulin heavy chain switch region polymorphisms are not associated with type 1 diabetes. 290 16

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQ alpha, DQ beta and DR beta chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQ beta restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7% vs 10.4%, respectively; p less than 10(-4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQ alpha-DQ beta patterns, only one of which was positively associated with diabetes. A DQ beta pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes.
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PMID:Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to type 1 (insulin-dependent) diabetes. 290 18


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