Class II HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies.
Class II HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies.
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DOI：
10.1111/j.2040-1124.2011.00139.x
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发表时间：
2012-02-20
影响因子：
3.2
通讯作者：
Japan Diabetes Society Committee on Type 1 Diabetes Mellitus Research
中科院分区：
文献类型：
--
作者：
Tsutsumi C;Imagawa A;Ikegami H;Makino H;Kobayashi T;Hanafusa T;Japan Diabetes Society Committee on Type 1 Diabetes Mellitus Research
目的/简介：暴发性1型糖尿病是1型糖尿病的一种亚型，其特征是在几天内显著突然发生胰岛素缺乏性高血糖。 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。材料和方法：我们分析了日本人群中207例暴发型1型糖尿病患者和325例对照受试者的HLA-DRB 1和DQB 1基因型及其单倍型。 结果：暴发型1型糖尿病患者DRB 1 * 04：05-DQB 1 *04：01和DRB 1 *09：01-DQB 1 *03：03单倍型频率显著高于对照组，DRB 1 *01：01-DQB 1 *05：01、DRB 1 *15：02-DQB 1 *06：01和DRB 1 *08：03-DQB 1 *06：01单倍型频率显著低于对照组。 组合分析显示，DRB 1 *04：05-DQB 1 *04：01 [比值比（OR）7.0]和DRB 1 *09：01-DQB 1 *03：03（OR 9.5）的纯合子频率在暴发型1型糖尿病患者中显著较高。在有限部分携带谷氨酸脱羧酶抗体（GADab; n = 25）的暴发性1型糖尿病患者中，DRB 1 *09：01-DQB 1 *03：03的频率显著高于对照受试者（44.0% vs 13.7%; Pc <0.05，OR 5.0），但DRB 1 * 04：05-DQB 1 *04：01的频率不显著高于对照受试者。 [对结果最后一行的更正，在2011年7月29日在线发布后添加：“OR 5.1”变更为“OR 5.0”。]结论：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，并暗示GADab阳性和GADab阴性暴发性1型糖尿病对疾病易感性的遗传贡献是不同的。 （J Diabetes Invest，doi：10.1111/j.2040 - 1124.2011.00139.x，2012）
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)
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