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  • 1
    Electronic Resource
    Electronic Resource
    HLA-DQ beta-chain restriction fragment length polymorphism as a risk marker in Type 1 (insulin-dependent) diabetes mellitus: a Finnish family study (1990)
    Springer
    Diabetologia 33 (1990), S. 357-362 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; restriction fragment length polymorphism ; HLA-DQ ; prediction of Type 1 diabetes ; genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Finnish Type 1 (insulin-dependent) diabetic families were analysed for HLA-DQ beta-chain polymorphism using a short intron-specific probe. A simple hybridization pattern was obtained in which all fragments were associated significantly with Type 1 diabetes. The simultaneous presence of two different risk markers, the allelic 12-kilobase and 4-kilobase fragments were strongly associated with Type 1 diabetes since 50% of the patients had this combination compared with only 2% of the control subjects. The cosegregated 7.5/3.0 kilobase fragments, which were associated with HLA-DR2 and DRw6 were not detected among the diabetic patients but were present in 48% of the control subjects. Our results provide further support for the location of susceptibility determining factors in the HLA-DQ gene area. The clear-cut, simple restriction fragment length polymorphism pattern obtained here, which bears a resemblance to a two allelic system, therefore makes this method applicable for estimating the risk of Type 1 diabetes at the population level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00404640
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    HLA haplotypes in Type 1 (insulin-dependent) diabetes mellitus: molecular analysis of the HLA-DQ locus (1992)
    Springer
    Diabetologia 35 (1992), S. 254-260 
    Details
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes mellitus ; HLA haplotypes ; HLA-DQ ; restriction fragment length polymorphism ; genetics ; disease susceptibility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In Caucasians the predisposition to Type 1 (insulin-dependent) diabetes mellitus has been shown to associate with HLA-DR3,DQw2 and DR4,DQw8 and with the presence of amino acids other than aspartic acid at position 57 on the HLA-DQβ chain. In Finland the haplotype-specific absolute risk for developing Type 1 diabetes differs between various DR3 and DR4 positive haplotypes. The aim of our present analysis was to find out whether this variation is attributable to polymorphism at the DQ locus. As part of a nationwide prospective study including 757 serologically HLA genotyped families, we determined HLA-DQα and DQβ restriction fragment polymorphisms in 17 selected families with important susceptibility haplotypes. Additionally, the DQA1 alleles were determined from 19 haplotypes using sequence-specific oligonucleotide probes, and the DQB1 second exon was sequenced from nine haplotypes. The DR3 as well as DR4 positive haplotypes frequently found in Type 1 diabetic patients showed no variation at the HLA-DQ locus, and they were DQw2 and DQw8, respectively. The absolute risk for Type 1 diabetes for DR4,DQw8 positive haplotypes A2,Cw4,Bw35,DR4 A3,Cw3,Bw62,DR4, A24,Cw7,Bw39,DR4, A2,Cw3,Bw62, DR4, and A2,Cw1,Bw56,DR4 was 35/100,000, 130/100,000, 166/100,000, 196/100,000, and 218/100,000, respectively. The absolute risks for DR3,DQw2 positive haplotypes A1, Cw7,B8,DR3 and A2,Cw7,B8,DR3 were 68/100,000 and 103/100,000, respectively. These results provide further evidence that not only the polymorphism at the DQ locus but also other genes of the haplotypes contribute to susceptibility to Type 1 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400926
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study (1995)
    Springer
    Diabetologia 38 (1995), S. 705-710 
    Details
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes mellitus ; cytomegalovirus ; pathogenesis ; prospective study ; ICA ; siblings.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37 %) siblings were constantly seronegative and 29 (63 %) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p 〈 0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells. [Diabetologia (1995) 38: 705–710]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401843
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Serological evaluation of the role of cytomegalovirus in the pathogenesis of IDDM: a prospective study (1995)
    Springer
    Diabetologia 38 (1995), S. 705-710 
    Details
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; cytomegalovirus ; pathogenesis ; prospective study ; ICA ; siblings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To study the possible temporal association between primary cytomegalovirus infection and the appearance of islet cell autoantibodies or the development of insulin-dependent diabetes mellitus (IDDM) cytomegalovirus antibodies were analysed from follow-up sera of 46 initially non-diabetic siblings of diabetic children who either manifested clinical IDDM (22 siblings) or turned islet cell antibody positive (24 siblings) during the prospective observation (mean follow-up time 2.9 years). Secondly, cytomegalovirus antibodies were analysed during pregnancy in 96 mothers whose child presented with IDDM before the age of 7 years and in 96 control mothers who gave birth to a non-diabetic child. Thirdly, a case-control series including 90 newly-diagnosed young children with IDDM and their 90 control subjects was analysed. No seroconversions were found in cytomegalovirus antibodies during the follow-up of the 46 siblings indicating no temporal association with islet cell antibody seroconversion or manifestation of clinical diabetes. During the follow-up 17 (37%) siblings were constantly seronegative and 29 (63%) seropositive for cytomegalovirus IgG and there was no difference between islet cell antibody positive and negative siblings. Cytomegalovirus IgG and IgM were not different in pregnant mothers who gave birth to a subsequently diabetic child compared to control mothers, or in newly-diagnosed diabetic children compared to control children. Cytomegalovirus IgA was higher in newly-diagnosed diabetic children than in control children (p〈0.005). This difference disappeared when only cytomegalovirus IgG positive individuals were analysed. No correlation was found between islet cell antibodies and cytomegalovirus antibodies in newly-diagnosed diabetic patients. The results do not support the hypothesis that primary cytomegalovirus infections could initiate the cascade leading to autoimmune destruction of the beta cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401843
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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