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Diabetologia
Published in: Diabetologia 12/2009

01-12-2009 | Article

Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset

Authors: Y. Kawabata, H. Ikegami, T. Awata, A. Imagawa, T. Maruyama, E. Kawasaki, S. Tanaka, A. Shimada, H. Osawa, T. Kobayashi, T. Hanafusa, K. Tokunaga, H. Makino, on behalf of the Committee on Type 1 Diabetes, Japan Diabetes Society

Published in: Diabetologia | Issue 12/2009

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Abstract

Aim/hypothesis

We sought to clarify similarities and differences in the contribution of HLA to genetic susceptibility to three subtypes of type 1 diabetes: acute-onset, fulminant and slowly progressive.

Methods

We genotyped 545 Japanese patients with type 1 diabetes (338 acute-onset, 80 fulminant, 127 slowly progressive) and 396 control participants at HLA-DRB1, -DQB1, -A, -B and -C, and at 101 candidate single nucleotide polymorphisms (SNPs) in an 8.5 Mb region of the extended HLA.

Results

DRB1*0405-DQB1*0401, DRB1*0802-DQB1*0302 and DRB1*0901-DQB1*0303 were associated with acute-onset type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 genotype achieving the highest odds ratio of 42.7. DRB1*1501-DQB1*0602 and DRB1*1502-DQB1*0601 were negatively associated with acute-onset type 1 diabetes. A similar tendency was observed for slowly progressive type 1 diabetes. In contrast, only DRB1*0405-DQB1*0401 was associated with fulminant type 1 diabetes, with the DRB1*0405-DQB1*0401/DRB1*0405-DQB1*0401 genotype showing the highest odds ratio of 11.2. DRB1*0802-DQB1*0302, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302 and DRB1*1501-DQB1*0602 were not associated with fulminant type 1 diabetes. The association of class I alleles and a panel of SNPs in an extended HLA region with fulminant type 1 diabetes was also different from that seen for the acute-onset and slowly progressive forms. The presence of both one and two susceptible haplotypes conferred susceptibility to slowly progressive type 1 diabetes, whereas the presence of two susceptible haplotypes was required to confer susceptibility to acute-onset and fulminant type 1 diabetes.

Conclusions/interpretation

These data suggest that HLA associations with fulminant type 1 diabetes are qualitatively different from those with other subtypes of type 1 diabetes, whereas the HLA contribution to slowly progressive type 1 diabetes is qualitatively similar to, but quantitatively different from, that in acute-onset type 1 diabetes.
Appendix
Available only for authorised users
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Metadata
Title
Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset
Authors
Y. Kawabata
H. Ikegami
T. Awata
A. Imagawa
T. Maruyama
E. Kawasaki
S. Tanaka
A. Shimada
H. Osawa
T. Kobayashi
T. Hanafusa
K. Tokunaga
H. Makino
on behalf of the Committee on Type 1 Diabetes, Japan Diabetes Society
Publication date
01-12-2009
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 12/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1539-9

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