PMID- 9314633
OWN - NLM
STAT- MEDLINE
DCOM- 19980116
LR  - 20190515
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 20
IP  - 10
DP  - 1997 Oct
TI  - Associations of GAD65- and IA-2- autoantibodies with genetic risk markers in 
      new-onset IDDM patients and their siblings. The Belgian Diabetes Registry.
PG  - 1547-52
AB  - 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.
FAU - Vandewalle, C L
AU  - Vandewalle CL
AD  - Diabetes Research Center, Vrije Universiteit Brussel, Belgium.
FAU - Falorni, A
AU  - Falorni A
FAU - Lernmark, A
AU  - Lernmark A
FAU - Goubert, P
AU  - Goubert P
FAU - Dorchy, H
AU  - Dorchy H
FAU - Coucke, W
AU  - Coucke W
FAU - Semakula, C
AU  - Semakula C
FAU - Van der Auwera, B
AU  - Van der Auwera B
FAU - Kaufman, L
AU  - Kaufman L
FAU - Schuit, F C
AU  - Schuit FC
FAU - Pipeleers, D G
AU  - Pipeleers DG
FAU - Gorus, F K
AU  - Gorus FK
LA  - eng
GR  - R01 DK026190/DK/NIDDK NIH HHS/United States
GR  - DK42654/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Autoantibodies)
RN  - 0 (Genetic Markers)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (ICA512 autoantibody)
RN  - 0 (Insulin)
RN  - EC 1.4.1.2 (Glutamate Dehydrogenase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Autoantibodies/*blood
MH  - Belgium
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/blood/*genetics/*immunology
MH  - Female
MH  - Genetic Markers
MH  - Genotype
MH  - Glutamate Dehydrogenase/*immunology
MH  - HLA-DQ Antigens/*genetics
MH  - Humans
MH  - Infant
MH  - Insulin/genetics
MH  - Male
MH  - *Nuclear Family
MH  - Registries
MH  - Risk Factors
EDAT- 1997/10/07 00:00
MHDA- 1997/10/07 00:01
CRDT- 1997/10/07 00:00
PHST- 1997/10/07 00:00 [pubmed]
PHST- 1997/10/07 00:01 [medline]
PHST- 1997/10/07 00:00 [entrez]
AID - 10.2337/diacare.20.10.1547 [doi]
PST - ppublish
SO  - Diabetes Care. 1997 Oct;20(10):1547-52. doi: 10.2337/diacare.20.10.1547.