The Onset of Diabetes in Three out of Four Sisters: A Japanese Family with Type 1 Diabetes. A Case Report
The Onset of Diabetes in Three out of Four Sisters: A Japanese Family with Type 1 Diabetes. A Case Report
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DOI：
10.1507/endocrj.k09e-079
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发表时间：
2009-09-01
影响因子：
2
通讯作者：
Maegawa, Hiroshi
中科院分区：
文献类型：
--
作者：
Kishi, Akio;Kawabata, Yumiko;Maegawa, Hiroshi
1A型糖尿病是一种自身免疫性疾病，其特征在于胰腺中产生胰岛素的β细胞的破坏。HLA-DR和-DQ基因被公认为与1型糖尿病风险增加相关。此外，CTLA 4的多态性已被报道与1型糖尿病和自身免疫性甲状腺疾病（AITD）的易感性相关。在高加索和日本人群中，1型糖尿病先证者的兄弟姐妹的终生风险远高于一般人群。然而，在日本，1型糖尿病的患病率不到大多数白人人口的十分之一，一个家庭中三个或更多兄弟姐妹患1型糖尿病的情况很少见。在这里，我们报告了一个日本家庭，其中1型糖尿病发生在三个兄弟姐妹中的四个姐妹篇。三个1型糖尿病先证者具有相同的HLA单倍型组合，DRB 1 *0405-DQB 1 *0401/DRB 1 *0802-DQB 1 *0302，在日本人群中，1型糖尿病患者比对照受试者更常见。关于CTLA 4的rs3087243（+6230G > A）多态性，第一个姐妹患有1型糖尿病和AITD，并且具有GG基因型，而患有1型糖尿病而没有AITD的第二和第三姐妹篇具有AG基因型。这是第一次报告的一个家庭，其中1A型糖尿病的发展，在三个兄弟姐妹。我们对所有家族成员进行了HLA-DR、-DQ和CTLA 4的遗传分析。即使在1型糖尿病患病率较低的国家，也应该监测糖尿病先证者兄弟姐妹是否发生1型糖尿病。
Type 1A diabetes is an autoimmune disease characterized by the destruction of insulin-producing beta-cells in the pancreas. The HLA-DR and -DQ genes are well established as being associated with increased risk for type 1 diabetes. Moreover, polymorphisms in CTLA4 have been reported to be associated with susceptibility to type 1 diabetes and autoimmune thyroid disease (AITD). In both Caucasian and Japanese populations, the lifetime risk in siblings of type 1 diabetic probands is much higher than that in general populations. However, in Japan, where the prevalence of type 1 diabetes is less than one-tenth that of most Caucasian populations, it is rare for type 1 diabetes to develop in three or more siblings within a family. Here, we report a Japanese family in which type 1 diabetes occurred in three siblings amongst four sisters. Three probands of type 1 diabetes had the same combination of HLA haplotypes, DRB1*0405-DQB1*0401/DRB1*0802-DQB1*0302, which occurs significantly more often in type 1 diabetes patients than in control subjects in the Japanese population. With respect to the rs3087243 (+6230G > A) polymorphism of CTLA4, the first sister had type 1 diabetes and AITD and had the GG genotype, whereas the second and third sisters, who had type 1 diabetes without AITD, had the AG genotype. This is the first report of a family in which type 1A diabetes developed in three siblings. We performed genetic analysis of HLA-DR, -DQ, and CTLA4 in all family members. Even in a country where the prevalence of type 1 diabetes is low, diabetic proband siblings should be monitored for the onset of type 1 diabetes.