The study on significance of imprinting gene(s) for the development of insulin-dependent diabetes mellitus in children

印迹基因在儿童胰岛素依赖型糖尿病发生中的意义研究

• 批准号: 12670775
• 负责人: YOKOTA Yukifumi
• 金额: $ 2.18万
• 依托单位: KITASATO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670775/
• 关键词: Type 1 diabetes mellitus; Susceptibility gene(s); HLA-DQ gene; HLA-DR gene; CTLA-4 gene polymorphism; NeuroD; BETA2 gene; IDDMK1, 2-22 gene; Family history of diabetes; I型糖尿病; スーパー抗原活性; インプリンティング; 小児1型糖尿病; HLA遺伝子; HLA-DR抗原遺伝子

We have studied the family history of diabetes mellitus among first degree relatives of type 1 diabetes mellitus in children. We found the family history of diabetes was significantly higher in slowly progressing type 1 diabetes than acutely onset diabetes. Moreover, incidence of mother's diabetes was significantly higher than that of father. To role out the possibility of epigenetic mechanism, such as imprinting of susceptibility gene for type 1 diabetes, we extracted DNA from parents and sibling of type 1 diabetic children. This study was approved by the B Kitasato Ethnic committee. Twenty set of parents and sibling were agreed to joint his study. We have analyzed HLA DQ-β, -α gene, DR-β gene, CTLA-4 gene, NeuroD/BETA2 gene, IDDHK1, 2-22 gene in children with type 1 diabetes and their parents and sibling whether susceptibility genes derived from mother or father. The absolute number of parents were too small to draw conclusions, susceptible HLA genes derived more from the father than the mother in type 1 diabetic children.

我们对儿童1型糖尿病一级亲属的糖尿病家族史进行了研究。我们发现缓慢进展的1型糖尿病患者的糖尿病家族史显著高于急性发病的1型糖尿病患者。此外，母亲的糖尿病发病率明显高于父亲。为了揭示表观遗传机制的可能性，例如1型糖尿病易感基因的印记，我们从1型糖尿病儿童的父母和兄弟姐妹中提取了DNA。这项研究得到了北里民族委员会的批准。20对父母和兄弟姐妹同意与他一起学习。我们分析了1型糖尿病儿童及其父母兄弟姐妹的HLADQ-β，-α基因、DR-β基因、CTLA-4基因、NeuroD/Beta2基因、IDDHK1、2-22基因是否来源于母亲或父亲。父母的绝对数量太少，无法得出结论，在1型糖尿病儿童中，易感基因来自父亲的比来自母亲的更多。

项目成果

Kawasaki E, Sera Y, et al.: "Identification and functional analysis of mutations in the Hepatocyte Nuclear Factor-1αin Japanese diabetic patients initially classified as having Type 1 diabetes"J Clin Endocrinol Metab. 85(1). 331-335 (2000)

Kawasaki E、Sera Y 等人：“最初分类为 1 型糖尿病的日本糖尿病患者中肝细胞核因子 1α 突变的鉴定和功能分析”J Clin Endocrinol Metab 85(1)。 ）

Ihara K, Ahmed S, et al.: "Association studies of CTLA-4,CD28,and ICOS gene polymorphisms with type 1 diabetes in the Japanese population"Immunogenetics. 53. 447-454 (2001)

Ihara K、Ahmed S 等人：“CTLA-4、CD28 和 ICOS 基因多态性与日本人群 1 型糖尿病的关联研究”免疫遗传学。

Matsuura N, Yokota Y, et al.: "Initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children"Pediatric Diabtes. 2(4). 160-169 (2001)

Matsuura N、Yokota Y 等人：“日本儿童 1 型糖尿病家族史的初步目标和影响”小儿糖尿病。

Ahmed S, Ihara K, et al.: "Association study between CD30 and CD30 ligand genes and type 1 diabetes in the Japanese population"Genes Immunity. 3. 96-101 (2002)

Ahmed S、Ihara K 等人：“日本人群中 CD30 和 CD30 配体基因与 1 型糖尿病之间的关联研究”基因免疫。

西村真里子, 横田行史, 他: "新生児マススクリーニングで一過性高TSH血症と初期診断され,思春期に異所性甲状腺によるクレチン症と診断された1例"日本マス・スクリーニング学会誌. 10(3). 51-54 (2000)

Mariko Nishimura、Yukifumi Yokota 等人：“一例在新生儿大规模筛查中最初诊断为短暂性高 TSH 血症，并在青春期因异位甲状腺而诊断为克汀病”，《日本大规模筛查协会杂志》10(3)。 2000）