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)

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.
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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.
Diabetes Res 1991 Apr
PMID:Frequencies of HLA-DR3, -DR4, -B8 and -Bw62 in diabetic children diagnosed between 1960 and 1990. 180 81

Serum levels of immunoglobulins G, A and M were quantitatively measured at diagnosis and at regular intervals for four years in 92 type I (insulin-dependent) diabetes patients. The patients were 0.8-15.99 years of age at diagnosis. Thirty-six of them got diabetes during periods of high incidence (the "epidemic" group) and 56 of them were diagnosed during periods of seemingly low incidence (the non-"epidemic" patients). Fifty percent (18/36) of the "epidemic" group had infections less than two months preceding diagnosis as compared to 29% (16/56) (p less than 0.01) of the non-"epidemic" patients. At diagnosis immunoglobulins G, and M in the "epidemic" group were 11.28 +/- 2.0 and 1.97 +/- 0.77 as compared to 9.9 +/- 2.3 (p less than 0.01) and 1.31 +/- 0.58 (p less than 0.001) respectively in the non-"epidemic" patients. The same highly significant differences were observed when mean values of IgG and IgM were compared between children who had infections less than two months before diagnosis and those without preceding infections. Except for slightly higher (p less than 0.12) total (OKT3) T-lymphocytes and higher (p less than 0.03) B-lymphocytes at diagnosis in the "epidemic" group, there were no significant differences in quantitative T- and B-lymphocyte subpopulations between various groups. 6.3% (2/32) of the patients who had preceding infections had HLA-DR3/non-DR4 genotypes as compared to 30.6% (15/49); p less than 0.001, of those patients without preceding infections.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Jan
PMID:Raised IgG and IgM in "epidemic" IDDM suggest that infections are responsible for the seasonality of type I diabetes. 181 92

Epidemiologic data suggest that having a parent with Type 2 (non-insulin-dependent) diabetes mellitus increases the risk for Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 diabetes and Type 2 diabetes. We contrast genetic risk factors in three sets of families, consisting of (1) a single Type 1 diabetic child (proband) and non-diabetic parents, (2) multiple Type 1 diabetic siblings and non-diabetic parents, and (3) at least one Type 1 diabetic child and at least one Type 2 diabetic parent. Previous studies have demonstrated that HLA region genes, which elevate the risk in Type 1 diabetes, have no significant effect with respect to the risk for developing Type 2 diabetes. An earlier report cited a contribution by the haptoglobin locus to genetic susceptibility for Type 2 diabetes. We provide evidence that a high risk HLA antigen (HLA-DR3) is decreased to a greater extent in Type 1 patients with a Type 2 parent than in Type 1 patients in which the parents are not diabetic. The role of HLA-DR4 is maintained in these families, with an unexpectedly significant increased rate of transmission of the HLA-DR4 allele from Type 2 parent to Type 1 offspring. The role of haptoglobin in these families does not appear to be important, either with respect to association with diabetes or with respect to linkage with a secondary susceptibility locus. These results indicate that families with a Type 2 parent and Type 1 child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility.
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PMID:Shared genetic susceptibility of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus: contributions of HLA and haptoglobin. 186 90

HLA-DR specificities in 72 Addison's (AD) patients and 808 local controls were compared. We confirmed earlier reports that the HLA-DR3 specificity is significantly increased in AD patients. In our study a relative risk of 3.4 chi 2 = 22.5; pc = 0.01) for the disease was calculated. Analysis of HLA-DQB1 alleles in DR4+ Addison's patients with diabetes mellitus (N = 6) and without IDDM (14 of 18 individuals tested) revealed that the HLA-DQw8 allele (DQB1*0302) was significantly increased in AD patients with IDDM (chi 2 = 13.5; p = 0.001); conversely, a clustering of the HLA-DQw7 allele was detected in DR4+ Addison's patients without IDDM. We thus conclude that particular polymorphic alleles corresponding to non-charged amino acids at position 57 of the HLA-DQ beta-chain [non-Asp-57 alleles] are associated with IDDM also in Addison's patients.
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PMID:The HLA-DQ beta non-Asp-57 allele: a predictor of future insulin-dependent diabetes mellitus in patients with autoimmune Addison's disease. 187 64

The frequency of HLA-DR antigens, as well as the prevalence of islet cell insulin autoantibodies and other autoimmunity disorders, were investigated in Tunisian patients with insulin-dependent diabetes mellitus (IDDM) and were compared with family members (sibs) and healthy control subjects. Cytoplasmic islet cell autoantibodies (ICA) were found in 79 of 175 (45.1%) patients with IDDM, in 23 of 126 (18.25%) unaffected first degree relatives of type I diabetes patients and in only two of 146 (1.3%) control subjects. In 79 ICA positive patients with IDDM, 46.8% presented other evidence of autoimmunity by testing for specific autoantibodies. Insulin autoantibodies were found in 86.9% of healthy ICA-positive sibs. A good correlation between HLA-DR3/DR4 heterozygous phenotypes and the presence of ICA in patients with IDDM and their unaffected sibs was observed in the Tunisian population. In fact, this heterozygous phenotype is found in 63.3% of ICA-positive diabetic patients and in 44.4% of ICA-positive unaffected sibs, whereas, HLA-DR3/DR4 antigens were noted in only 22.9% of ICA-negative diabetic patients and in no ICA-negative unaffected sibs. In these studies, we also summarized the distribution of HLA-DR antigens in patients with IDDM who presented autoimmune disorders other than ICA.
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PMID:Immunogenetic heterogeneity in type I (insulin-dependent) diabetes among the Tunisian population. HLA-DR antigens and organ-specific autoantibodies (family study). 191 Apr 27

Studies of various insulin-dependent diabetes mellitus (IDDM) populations have shown that certain HLA antigens confer a high risk of developing disease. There is very little information concerning the distribution of HLA antigens in type 1 diabetes in the Turkish population. In this study, the HLA types of 75 patients and 50 controls were investigated. HLA-DR3 and HLA-DR4 were found more frequently in the IDDM cases (p = 0.0018 and 0.0119, respectively). DR3/DR4, although more frequent, did not achieve statistical significance. The decreased frequencies of DR1 and DR2 in the IDDM population were not significant whereas the DR7 was found to be significantly decreased (p = 0.025). The younger age of onset was strongly associated with DR4 (p = 0.0029). DR3 was more common among the male and DR4 in the female patients. However, the differences were not significant.
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PMID:The type 1 diabetes and HLA-DR in Turkey. 191 1

We describe 13 cases of inflammatory lesion of breast lobules in young and middle-aged women, presenting as breast lumps, with, in five cases, associated breast pain. The patient with the most florid bilateral disease subsequently developed Hashimoto's thyroiditis. This prompted us to consider an autoimmune pathogenesis for all the breast lesions. We confirm a previously documented association of such breast lesions with diabetes mellitus and review the evidence for a possible HLA association. Increased HLA-DR expression by breast epithelial cells was observed in cases available for study. Of the seven patients screened for circulating autoantibodies, three had none, one had smooth muscle antibodies, one parietal cell, one parietal cell and thyroid microsomal, and the seventh had the thyroid autoantibodies expected in Hashimoto's disease. Five of seven patients whose HLA-status was determined were HLA-DR3, 4 or 5 positive, either singly or in combination. Immunophenotypic analysis of the mammary lymphoid infiltrate showed that the majority of infiltrating lymphocytes were B-cells.
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PMID:Sclerosing lymphocytic lobulitis of the breast--evidence for an autoimmune pathogenesis. 191 85

The aetiology of insulin-dependent diabetes (IDDM) involves genetic predisposition, a major component of which has been mapped in the HLA complex, near to or identical with genes encoding class II molecules. In Caucasian populations IDDM is strongly associated with the serologically defined HLA-DR3 and DR4 antigens, which are widely recognised as markers of susceptibility. The particularly high risk of DR3/DR4 heterozygotes suggests that susceptibility is determined by two genes acting synergistically. The development of recombinant DNA technology has allowed a finer description of the class II region and provided evidence that DQ rather than DR determinants may primarily influence IDDM susceptibility. The search for specific structural changes of the DQA and DQB genes has shown that susceptibility correlates with the absence of aspartic acid at position 57 on the DQ beta chain (DQ beta 57 Asp--) and/or the presence of arginine at position 52 on the DQ alpha chain (DQ alpha 52 Arg+). In Caucasians the formation of a putative DQ susceptibility molecule (DQ alpha 52 Arg+, DQ beta 57 Asp-) accounts best for the disease associations when transcomplementation molecules consisting of DQ alpha and beta chains encoded by different haplotypes are postulated to explain the excess risk of heterozygotes. The HLA-IDDM associations in the Japanese, however, are not explained by this model. These and other unresolved questions indicate that other residues of the DQ alpha and beta chains or other class II molecules (DR beta chains), as well as non-MHC genes, may also contribute to the susceptibility.
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PMID:The role of genetic predisposition to type I (insulin-dependent) diabetes mellitus. 193 Sep 40

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.
Diabetes 1991 Nov
PMID:Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study. 193 4


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