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  • 1
    Electronic Resource
    Electronic Resource
    Tumour necrosis factor-beta polymorphism is unlikely to determine susceptibility to Type 1 (insulin-dependent) diabetes mellitus (1991)
    Springer
    Diabetologia 34 (1991), S. 576-578 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; Indian Asian ; MHC ; tumour necrosis factor ; linkage disequilibrium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Tumour necrosis factor gene polymorphism has been proposed as a determinant of Type 1 (insulin-dependent) diabetes mellitus. Tumour necrosis factor-beta gene polymorphisms were analysed in 40 North Indian Asian Type 1 diabetic patients and 63 control subjects. A 5.5 kilobase gene fragment was significantly increased among the patients (82.5% vs 52%, p c〈0.01). A 10.5 kilobase fragment was significantly reduced among the patients (70% vs 90.5%, p c〈0.02). The 5.5 kilobase fragment was associated with DR3, and was not significantly increased among DR3-positive patients compared with DR3-positive control subjects. The 5.5 kilobase/5.5 kilobase genotype was increased among the diabetic subjects (30% vs 9.5%, p c〈0.03). The 10.5 kilobase/10.5 kilobase genotype was reduced among the diabetic subjects (17.5% vs 47.5%, p c〈0.02). The 5.5 kilobase/10.5 kilobase genotype was not significantly associated with disease. These findings contrast with those in a white Caucasian population, suggesting that tumour necrosis factor-beta polymorphisms do not predispose to Type 1 diabetes directly, but are in linkage disequilibrium with disease susceptibility alleles at other MHC loci.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400276
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  • 2
    Electronic Resource
    Electronic Resource
    Human leucocyte antigen and insulin gene regions and nephropathy in Type I diabetes (1999)
    Springer
    Diabetologia 42 (1999), S. 1017-1020 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; diabetic nephropathy ; human leucocyte antigen ; insulin gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. Methods. We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). Results. No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin ’ + ' and ’–' genotypes and alleles between the three diabetic cohorts. Conclusion/interpretation. Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom. [Diabetologia (1999) 42: 1017–1020]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051262
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  • 3
    Electronic Resource
    Electronic Resource
    Susceptibility to Type 1 (insulin-dependent) diabetes mellitus is determined by MHC class II molecules. What about DR4? (1993)
    Springer
    Diabetologia 36 (1993), S. 1210-1211 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401069
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  • 4
    Electronic Resource
    Electronic Resource
    Genetic and immunological characteristics of Type I diabetes mellitus in an Indo-Aryan population (2000)
    Springer
    Diabetologia 43 (2000), S. 450-456 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes, Indo-Aryan, immunogenetics, HLA genes, islet-related autoantibodies.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Our aim was to characterise the genetic and immunological features associated with Type I (insulin-dependent) diabetes mellitus in a cohort of Indo-Aryan children resident in the United Kingdom.¶Methods. Children with Type I diabetes (n = 53), unaffected first-degree relatives (n = 146) and unrelated healthy control children (n = 54) were typed for alleles of the HLA-DRB1, HLA-DQA1 and HLA-DQB1 genes. Islet cell antibodies and antibodies to glutamic acid decarboxylase, protein tyrosine phosphatase-2 (IA-2ic) and insulin were measured in the diabetic and control children.¶Results. The DRB1*03.DQA1*05.DQB1*02 haplotype was positively associated with the disease, occurring in 78 % of diabetic children compared with 22.6 % of healthy children (p c 〈 2.4 × 10–5). In simplex families, this haplotype was transmitted more frequently to the diabetic children than to their unaffected siblings (p 〈 1 × 10–4). The DRB1*04.DQA1* 03.DQB1*0302 haplotype was also transmitted preferentially to the diabetic probands (p 〈 0.025) but was not associated with disease in the case control study. Islet-related autoantibodies were detected in 89.6 % of diabetic patients compared with 11.8 % of control children (p 〈 1 × 10–6). Although protein tyrosine phosphatase-2 autoantibodies were detected more frequently among DRB1*04-positive diabetic patients compared with patients lacking this allele, the overall frequency of these autoantibodies was lower than observed in Europid diabetic subjects. This could reflect the absence of a disease association with DRB1*04 in the Indo-Aryan cohort.¶Conclusion/interpretation. Type I diabetes in our Indo-Aryan cohort is similar to the disease observed in Anglo-Europeans but has important immunogenetic differences. The low frequency of protein tyrosine phosphatase-2 autoantibodies among the Indo-Aryan diabetic children could have important implications for the design of future strategies for disease prediction in this population. [Diabetologia (2000) 43: 450–456]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051328
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  • 5
    Electronic Resource
    Electronic Resource
    Long-Term Expression of an HLA-DQ Molecule in the EBV-Transformed Bare Lymphocyte Cell Line, BLS-1, using a Plasmid Vector (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 55 (2002), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The HLA class II molecule, DQ6, confers strong natural protection against the development of type 1 diabetes. The mechanism of disease protection is unknown, but is likely to be related to the function of the molecule in antigen presentation. In order to investigate this function, we have created an in vitro model which expresses DQ6 in isolation by introducing the relevant DQ alleles into an Epstein–Barr virus (EBV)-transformed, human leucocyte antigen (HLA) class II-deficient B cell line, bare lymphocyte syndrome (BLS)-1. A recent report suggested that the expression of transferred genes in human EBV-transformed B cells might be limited in duration. We present a plasmid-based transfection method that allows long-term stable expression of the DQ molecule. The DQA1*0102 and DQB1*0602 alleles were cloned into the pCIneo expression vector and the constructs were introduced into BLS-1 by electroporation. Stable transfectants were selected using magnetic sorting and cloned by limiting dilution. Two clones were shown to express functionally active DQ6 molecules even after 14 months of continuous culture. These clones will be used in functional studies to investigate the antigen binding and T-cell activation properties of the DQ6 molecule.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01100.x
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  • 6
    Electronic Resource
    Electronic Resource
    Low C4 levels in Type 1 (insulin-dependent) diabetes (1987)
    Springer
    Diabetologia 30 (1987), S. 824-824 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275752
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