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
Publish Date: 2009/10/08
Volume: 52, Issue: 12, Pages: 2513-2521
Abstract
We genotyped 545 Japanese patients with type 1 diabetes 338 acuteonset 80 fulminant 127 slowly progressive and 396 control participants at HLADRB1 DQB1 A B and C and at 101 candidate single nucleotide polymorphisms SNPs in an 85 Mb region of the extended HLADRB10405DQB10401 DRB10802DQB10302 and DRB10901DQB10303 were associated with acuteonset type 1 diabetes with the DRB10405DQB10401/DRB10802DQB10302 genotype achieving the highest odds ratio of 427 DRB11501DQB10602 and DRB11502DQB10601 were negatively associated with acuteonset type 1 diabetes A similar tendency was observed for slowly progressive type 1 diabetes In contrast only DRB10405DQB10401 was associated with fulminant type 1 diabetes with the DRB10405DQB10401/DRB10405DQB10401 genotype showing the highest odds ratio of 112 DRB10802DQB10302 DRB10405DQB10401/DRB10802DQB10302 and DRB11501DQB10602 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 acuteonset 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 acuteonset and fulminant type 1 diabetesThese 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 acuteonset type 1 diabetes
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