The Onset of Diabetes in Three out of Four Sisters: A Japanese Family with Type 1 Diabetes. A Case Report

Endocrine Journal

Takeshi YOSHIZAKI²  Yuki TANAKA²  Hiroshi MAEGAWA²  Takashi UZU²  Tamaki IWAI²  Yoshihiko NISHIO²  Satoshi UGI²  Hiroshi IKEGAMI¹  Atsunori KASHIWAGI²  Akio KISHI²  Yumiko KAWABATA¹ 

[1] Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine;Department of Medicine, Shiga University of Medical Science

关键词: Type 1 diabetes;    Sibling;    Japanese;    HLA;    CTLA4;   

DOI  :  10.1507/endocrj.K09E-079

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(22)Cited-By(1)Type 1A diabetes is an autoimmune disease characterized by the destruction of insulin-producing β-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.

【 授权许可】

Unknown