Department of Internal Medicine (I), Osaka Medical College.
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University.
J Diabetes Investig. 2012 Feb 20;3(1):62-9. doi: 10.1111/j.2040-1124.2011.00139.x.
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.
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.
The frequencies of the DRB104:05-DQB104:01 and DRB109:01-DQB103:03 haplotypes were significantly higher, and those of the DRB101:01-DQB105:01, DRB115:02-DQB106:01 and DRB108:03-DQB106:01 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 DRB104:05-DQB104:01 [odds ratio (OR) 7.0] and DRB109:01-DQB103:03 (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 DRB109:01-DQB103:03, but not DRB104:05-DQB104:01, 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".]
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).
目的/引言：暴发性 1 型糖尿病是 1 型糖尿病的一个亚型，其特征为在数天内出现胰岛素缺乏性高血糖的显著急剧发作。本研究的目的是阐明迄今为止大量暴发性 1 型糖尿病患者的特征性 II 类 HLA 基因型。
我们分析了 207 例暴发性 1 型糖尿病患者和 325 名日本对照者的 HLA-DRB1 和 DQB1 基因型及其单倍型。
DRB104:05-DQB104:01 和 DRB109:01-DQB103:03 单倍型的频率显著升高，而 DRB101:01-DQB105:01、DRB115:02-DQB106:01 和 DRB108:03-DQB106:01 单倍型的频率在暴发性 1 型糖尿病患者中显著降低。组合分析显示，DRB104:05-DQB104:01（比值比[OR]7.0）和 DRB109:01-DQB103:03（OR 9.5）纯合子的频率在暴发性 1 型糖尿病患者中显著升高。在暴发性 1 型糖尿病伴谷氨酸脱羧酶（GADab）抗体的有限部分患者中（n=25），DRB109:01-DQB103:03 的频率显著高于对照组（44.0% vs 13.7%；Pc<0.05，OR 5.0）。[对结果部分的最后一行进行更正，在线发表 2011 年 7 月 29 日之后添加："OR 5.1"更改为"OR 5.0"。]
我们的大规模研究显示了暴发性 1 型糖尿病的特征性 II 类 HLA 基因型，并提示疾病易感性的遗传贡献在 GADab 阳性和 GADab 阴性暴发性 1 型糖尿病之间存在差异。（糖尿病研究与临床实践，doi：10.1111/j.2040-1124.2011.00139.x，2012）。
