Class II HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies.
Aims/Introduction:  Fulminant type 1 diabetes is a subtype of type 1 diabetes characterized by a remarkably abrupt onset of insulin-deficient hyperglycemia within a few days. The aim of the present study was to clarify characteristic class II HLA genotypes in a large number of patients with fulminant type 1 diabetes to date.


METHODS
We analyzed the HLA-DRB1 and DQB1 genotypes, and their haplotypes in 207 patients with fulminant type 1 diabetes and 325 control subjects in the Japanese population.


RESULTS
The frequencies of the DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes were significantly higher, and those of the DRB1*01:01-DQB1*05:01, DRB1*15:02-DQB1*06:01 and DRB1*08:03-DQB1*06:01 haplotypes were significantly lower in patients with fulminant type 1 diabetes than in the control subjects. Combination analysis showed that the frequencies of homozygotes with DRB1*04:05-DQB1*04:01 [odds ratio (OR) 7.0] and DRB1*09:01-DQB1*03:03 (OR 9.5) were significantly higher in patients with fulminant type 1 diabetes. Within a limited portion of patients with fulminant type 1 diabetes with antibodies to glutamic acid decarboxylase (GADab; n = 25), the frequency of DRB1*09:01-DQB1*03:03, but not DRB1*04:05-DQB1*04:01, was significantly higher than in control subjects (44.0% vs 13.7%; Pc < 0.05, OR 5.0). [Correction to last line of RESULTS, added after online publication 29 July 2011: "OR 5.1" is changed to "OR 5.0".]


CONCLUSIONS
Our large-scale study showed the characteristic class II HLA genotypes in fulminant type 1 diabetes, and implicated that genetic contribution to disease susceptibility is distinct between GADab-positive and GADab-negative fulminant type 1 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00139.x, 2012).
Department of Internal Medicine (I), Osaka Medical College.
Chiharu
C
Tsutsumi
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University.
Akihisa
A
Imagawa
Department of Endocrinology, Metabolism, and Diabetes, Kinki University School of Medicine, Osaka.
Hiroshi
H
Ikegami
Shiraishi Hospital Diabetes Center, Ehime.
Hideichi
H
Makino
Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
Tetsuro
T
Kobayashi
Department of Internal Medicine (I), Osaka Medical College.
Toshiaki
T
Hanafusa
Fulminant type 1 diabetes; Glutamic acid decarboxylase; HLA