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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; genetic susceptibility or resistance ; HLA-DQ molecules ; preferential peptide presentation ; beta-cell reactive T cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Genes in the HLA complex are by far the most important in determining genetic predisposition or resistance to Type 1 (insulin-dependent) diabetes mellitus. In this review evidence is presented that the HLA genes mainly involved are those encoding some particular HLA-DQ molecules. Both among Black, Caucasian and Japanese subjects particular cis or trans encoded DQ molecules are significantly associated with susceptibility, while others are associated with resistance. A varying degree of susceptibility or resistance seems to be conferred by these DQ molecules, where those determining resistance are dominant over those determining susceptibility. The degree of genetic predisposition to develop Type 1 diabetes carried by an individual would therefore be the result of his or her particular combination of DQ molecules. A primary association to particular DQ molecules explains previously found associations to other HLA complex genes by linkage disequilibrium. Some mechanisms by which particular DQ molecules may determine susceptibility or resistance are also discussed. Potential islet beta-cell reactive CD4+ T-cells may escape negative selection (deletion) in the thymus, but normally become anergized or remain ignorant extra-thymically. However, under particular circumstances they may be triggered. The DQ molecules associated with Type 1 diabetes susceptibility may preferentially bind and present triggering and/or beta-cell derived peptides to such T cells, causing beta-cell destruction. The finding that particular DQ molecules determine susceptibility may lead to new methods of preventing development of Type 1 diabetes in susceptible individuals.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin gene polymorphism ; HLA class II genotypes ; transracial comparison ; IDDM ; genetic susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have suggested an association between polymorphisms in the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Most of the studies so far have been performed in Caucasoid populations. We have investigated 418 random IDDM patients and 422 healthy control subjects from three different ethnic groups; Tanzanian blacks, Norwegian Caucasians and Japanese orientals. Our data suggest that polymorphisms in the insulin gene region confer susceptibility to IDDM in Caucasians, and that a similar tendency though not statistically significant is observed among Tanzanian blacks, while no significant contribution is seen among Japanese orientals. We further demonstrate that the disease-associated genotype INS +/+ confers susceptibility independently of HLA class II alleles associated with IDDM. Compared to the contribution of particular HLA-DQ alleles in IDDM susceptibility, the additional risk conferred by the insulin gene region polymorphism is, however, small. Genotyping of the insulin gene region will therefore most probably not be a useful tool in the prediction of IDDM.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Insulin gene polymorphism, HLA class II genotypes, transracial comparison, IDDM, genetic susceptibility.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have suggested an association between polymorphisms in the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Most of the studies so far have been performed in Caucasoid populations. We have investigated 418 random IDDM patients and 422 healthy control subjects from three different ethnic groups; Tanzanian blacks, Norwegian Caucasians and Japanese orientals. Our data suggest that polymorphisms in the insulin gene region confer susceptibility to IDDM in Caucasians, and that a similar tendency though not statistically significant is observed among Tanzanian blacks, while no significant contribution is seen among Japanese orientals. We further demonstrate that the disease-associated genotype INS+/+ confers susceptibility independently of HLA class II alleles associated with IDDM. Compared to the contribution of particular HLA-DQ alleles in IDDM susceptibility, the additional risk conferred by the insulin gene region polymorphism is, however, small. Genotyping of the insulin gene region will therefore most probably not be a useful tool in the prediction of IDDM. [Diabetologia (1994) 37: Wingdingsx–Wingdingsx] [Diabetologia (1994) 37: 745–749]
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 38 (1993), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the present study we characterized the frequencies of two polymorphisms within the MHC-linked heat shock protein (HSP) 70 genes in patients with insulin-dependent diabetes mellitus (IDDM) (n= 114) and healthy control individuals (n = 110). Significant differences in genotype and allelic frequencies were observed for both polymorphisms between randomly selected patients and controls. However, for the HSP70-2 polymorphisms this was solely due to linkage disequilibrium with DR3. The rare HSP70-Hom 2-allele was significantly more frequent in controls than in patients. It showed strong association with certain tumour necrosis factor (TNF) (class III) and HLA-B and -A (class I) alleles independent of HLA-DQ and -DR alleles. By typing 257 individuals from 55 IDDM multiple-case families two extended MHC-haplotypes, including class II-, TNF- and class I-markers, carrying the rare HSP70-Hom allele were defined. One was only transmitted to diabetic offspring, whereas the other was only transmitted to unaffected offspring. The functional implication of the polymorphism in the heat shock-inducible HSP70-2 gene was analysed by studying HSP70-2 mRNA expression after heat shock in peripheral blood mononuclear cells from individuals with different HSP70-2 genotypes. Preliminary data showed that individuals homozygous for the PstI 8.5-kb allele consistently had slightly lower expression than heterozygous and 9·0-kb homozygous individuals.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 36 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Two new TCRVβ coding region polymorphisms were identified: Vβ6.9a/b and Vβ21.4a/b. In both cases, a single nucleotide difference gives rise to an amino acid exchange. Genomic typing by the PCR/sequence-specific oligonucleotide probing technique was performed to study a possible contribution of these two new polymorphisms in susceptibility to autoimmune diseases. However, there was no association with insulin-dependent diabetes mellitus, rheumatoid arthritis, juvenile rheumatoid arthritis, multiple sclerosis, myasthenia gravis or coeliac disease. On the other hand, significant differences were found between Caucasoid and Oriental populations in frequencies of the Vβ6.9 and Vβ21.4 alleles.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 356 (1992), S. 23-23 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] SIR - Wank and Thomssen1 have suggested that there is an increased risk of developing squamous cell carcinoma of the cervix for individuals carrying the HLA-DQw3 antigen. They reported that of 66 patients tested, 87.7% carried HLA-DQw3 compared to 50.4% in controls (relative risk (RR) = 7.1, ...
    Type of Medium: Electronic Resource
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