Clinical and Genetic Characteristics of Autoimmune Polyglandular Syndrome Type 3 Variant in the Japanese Population
Clinical and Genetic Characteristics of Autoimmune Polyglandular Syndrome Type 3 Variant in the Japanese Population
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DOI：
10.1210/jc.2011-3109
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Kawakami, Atsushi
中科院分区：
文献类型：
--
作者：
Horie, Ichiro;Kawasaki, Eiji;Kawakami, Atsushi
目的：1型糖尿病（T1 D）通常与自身免疫性甲状腺疾病（AITD）相关，患者中T1 D和AITD的发生被定义为自身免疫性多腺体综合征3型变体（APS 3v）。我们的目的是阐明日本人群中APS 3v患者和T1 D患者（无AITD [T1 D/AITD（-）]）的临床和遗传特征的差异。设计/患者：我们的研究对象是从1983年至今在长崎大学医院连续诊断的54例APS 3v患者和143例T1 D/AITD（-）患者。结果：与T1 D/AITD（-）患者相比，在APS 3v患者中观察到显著的女性优势、T1 D发病缓慢且年龄较大以及谷氨酸脱羧酶自身抗体的患病率较高。在APS 3v患者中，T1 D的发病年龄较大与慢发型T1 D的比例较高相关。在日本T1 D患者的两种主要易感人类白细胞抗原（HLA）II类单倍型中，DRB 1 *0405-DQB 1 *0401与APS 3v患者相关，而DRB 1 *0901-DQB 1 *0303与APS 3v患者无关。此外，DRB 1 *0803-DQB 1 *0601在APS 3v患者中没有保护作用。CTLA 4基因+49G>A和+6230G>A多态性中GG基因型的频率在T1 D/AITD（-）患者中显著高于对照组，但在APS 3v患者中不显著。总之，我们发现日本人群中APS 3v患者和T1 D/AITD（-）患者的临床和遗传特征存在显著差异，两组临床特征的差异可能反映了不同的遗传背景，包括HLA DRB 1-DQB 1单倍型和CTLA 4基因多态性。（临床内分泌代谢杂志97：E1043-E1050，2012）
Objective: Type 1 diabetes (T1D) is commonly associated with autoimmune thyroid disease (AITD), and the occurrence of both T1D and AITD in a patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v). We aimed to clarify the differences in the clinical and genetic characteristics of APS3v patients and T1D patients without AITD [T1D/AITD(-)] in the Japanese population.Design/Patients: Our subjects were 54 APS3v patients and 143 T1D/AITD(-) patients who were consecutively diagnosed at Nagasaki University Hospital from 1983 to the present.Results: A remarkable female predominance, a slow and older age onset of T1D, and a higher prevalence of glutamic acid decarboxylase autoantibodies were observed in APS3v patients compared to T1D/AITD(-) patients. The older onset age of T1D in APS3v patients was associated with a higher proportion of slow-onset T1D. Among the two major susceptible human leukocyte antigen (HLA) class II haplotypes in Japanese T1D, DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, was associated with APS3v patients. Furthermore, DRB1*0803-DQB1*0601 was not protective in patients with APS3v. The frequencies of the GG genotype in +49G>A and +6230G>A polymorphism in the CTLA4 gene were significantly higher in T1D/AITD(-) patients, but not in APS3v patients, compared to control subjects.Conclusions: In conclusion, we found notable differences in the clinical and genetic characteristics of APS3v patients and T1D/AITD(-) patients in the Japanese population, and the differences in the clinical characteristics between the two groups may reflect distinct genetic backgrounds including the HLA DRB1-DQB1 haplotypes and CTLA4 gene polymorphisms. (J Clin Endocrinol Metab 97: E1043-E1050, 2012)