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Associations of GAD65- and IA-2-autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings : The Belgian Diabetes Registry

Vandewalle, Christina L. ; Falorni, Alberto ; Lernmark, Åke LU orcid ; Goubert, Patrick ; Dorchy, Harry ; Coucke, Willy ; Semakula, Crispin ; Van Der Auwera, Bart ; Kaufman, Leon and Schuit, Frans C. , et al. (1997) In Diabetes Care 20(10). p.1547-1552
Abstract

OBJECTIVE - To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS - Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS - At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the... (More)

OBJECTIVE - To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS - Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS - At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the 20- to 39-year age-group: 1) their prevalence was higher in carriers of DQA1 *0301-DQB1 *0302 (88 vs. 73% in non[DQA1 *0301-DQB1 *0302], P = 0.001), and 2) an association was found in patients lacking this haplotype but carrying DQA1 *0501-DQB1 *0201, together with INS I/I (87 vs. 54% vs. non[INS I/I], P = 0.003). Siblings of IDDM patients also presented the association of GAD65-Abs with DQA1*0301-DQB1*0302 (13 vs. 2% non[DQA1 *0301 -DQB1 *0302], P < 0.001), while associations with the second genetic risk group could not yet be assessed. At the onset of IDDM, IA-2-Ab prevalence was higher in carriers of DQA1 *0301-DQB1*0302 (69 vs. 39% non[DQA1 *0301-DQB1 *0302], P < 0.001) but not of DQA1 *0501-DQB1*0201 or INS I/I. This association was present in both the 0- to 19- and the 20- to 39-year age-groups. It was also found in siblings of IDDM patients (4 vs. 0% non[DQA1 *0301-DQB1 *0302], P < 0.001). CONCLUSIONS - Both GAD65- and IA- 2-Abs exhibit higher prevalences in presence of HLA-DQ- and/or INS-genetic risk markers. Their respective associations differ with age at clinical onset, suggesting a possible usefulness in the identification of subgroups in this heterogeneous disease.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
20
issue
10
pages
1547 - 1552
publisher
American Diabetes Association
external identifiers
  • scopus:0030770285
  • pmid:9314633
ISSN
0149-5992
DOI
10.2337/diacare.20.10.1547
language
English
LU publication?
no
id
e967ed8a-4577-4c8a-adf8-1e2b4ea5b462
date added to LUP
2019-07-01 13:17:36
date last changed
2024-03-13 08:03:15
@article{e967ed8a-4577-4c8a-adf8-1e2b4ea5b462,
  abstract     = {{<p>OBJECTIVE - To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS - Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS - At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the 20- to 39-year age-group: 1) their prevalence was higher in carriers of DQA1 *0301-DQB1 *0302 (88 vs. 73% in non[DQA1 *0301-DQB1 *0302], P = 0.001), and 2) an association was found in patients lacking this haplotype but carrying DQA1 *0501-DQB1 *0201, together with INS I/I (87 vs. 54% vs. non[INS I/I], P = 0.003). Siblings of IDDM patients also presented the association of GAD65-Abs with DQA1*0301-DQB1*0302 (13 vs. 2% non[DQA1 *0301 -DQB1 *0302], P &lt; 0.001), while associations with the second genetic risk group could not yet be assessed. At the onset of IDDM, IA-2-Ab prevalence was higher in carriers of DQA1 *0301-DQB1*0302 (69 vs. 39% non[DQA1 *0301-DQB1 *0302], P &lt; 0.001) but not of DQA1 *0501-DQB1*0201 or INS I/I. This association was present in both the 0- to 19- and the 20- to 39-year age-groups. It was also found in siblings of IDDM patients (4 vs. 0% non[DQA1 *0301-DQB1 *0302], P &lt; 0.001). CONCLUSIONS - Both GAD65- and IA- 2-Abs exhibit higher prevalences in presence of HLA-DQ- and/or INS-genetic risk markers. Their respective associations differ with age at clinical onset, suggesting a possible usefulness in the identification of subgroups in this heterogeneous disease.</p>}},
  author       = {{Vandewalle, Christina L. and Falorni, Alberto and Lernmark, Åke and Goubert, Patrick and Dorchy, Harry and Coucke, Willy and Semakula, Crispin and Van Der Auwera, Bart and Kaufman, Leon and Schuit, Frans C. and Pipeleers, Daniël G. and Gorus, Frans K.}},
  issn         = {{0149-5992}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{10}},
  pages        = {{1547--1552}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Associations of GAD65- and IA-2-autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings : The Belgian Diabetes Registry}},
  url          = {{http://dx.doi.org/10.2337/diacare.20.10.1547}},
  doi          = {{10.2337/diacare.20.10.1547}},
  volume       = {{20}},
  year         = {{1997}},
}