See Appendix for members of the research Committee of type 1 Diabetes, Japan Diabetes Society.
Class II HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies
Article first published online: 28 JUN 2011
© 2011 Asian Association for the Study of Diabetes and Blackwell Publishing Asia Pty Ltd
Journal of Diabetes Investigation
Volume 3, Issue 1, pages 62–69, February 2012
How to Cite
Tsutsumi, C., Imagawa, A., Ikegami, H., Makino, H., Kobayashi, T., Hanafusa, T. and on behalf of the Japan Diabetes Society Committee on Type 1 Diabetes Mellitus Research (2012), Class II HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies. Journal of Diabetes Investigation, 3: 62–69. doi: 10.1111/j.2040-1124.2011.00139.x
- Issue published online: 20 FEB 2012
- Article first published online: 28 JUN 2011
- Received 3 February 2011; revised 7 May 2011; accepted 8 May 2011
- Fulminant type 1 diabetes;
- Glutamic acid decarboxylase
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.
Materials and 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)