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  • 1
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; HLA-DQ ; racial studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 DQα, DQβ and DRβ 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 DQβ 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〈10−4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQα-DQβ patterns, only one of which was positively associated with diabetes. A DQβ 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.
    Type of Medium: Electronic Resource
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  • 2
    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
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  • 3
    ISSN: 1432-0428
    Keywords: Type 1 diabetes ; trans-racial studies ; DNA ; gene mapping ; HLA ; MHC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A major component of inherited susceptibility to Type 1 (insulin-dependent) diabetes mellitus has been mapped to the major histocompatibility complex. Certain gene alleles in this region determine susceptibility and resistance to the disease. Mapping of susceptibility is hindered by the limitations of conventional tissue typing techniques, and by strong linkage disequilibrium within this part of the genome. Recombinant DNA technology and trans-racial studies have been used to allow finer mapping of genetic predisposition to Type 1 diabetes. These techniques have localised alleles encoding susceptibility and resistance to the DQ region. Other alleles determining disease susceptibility remain poorly localised.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Trans-racial studies ; North Indians ; gene probing ; HLA-DQ ; Type 1 (insulin-dependent) diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Trans-racial analysis of disease associations has improved mapping of MHC-linked susceptibility to Type 1 (insulin-dependent) diabetes mellitus. In this study the contributions of the MHC class II DQA1 and DQB1 genes were investigated. Sequence-specific oligonucleotide gene probing in Type 1 diabetic and control subjects of North Indian origin supported the DQw1.18 allele of the DQB1 gene as a determinant of inherited protection against Type 1 diabetes (RR=0.12, p c〈0.05). The A3 allele of the DQA1 gene was positively associated with the disease, (RR=3.6, p c〈0.05), as was the DQw2 allele of the DQB1 gene (RR=4.6, p c〈0.01). Trans-racial comparison of these disease associations indicates that DQ alleles may directly determine an element of inherited susceptibility to Type 1 diabetes.
    Type of Medium: Electronic Resource
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