Pathophysiology and pathogenesis of childhood-onset insulin-dependent diabetes mellitus (IDDM)

儿童期发病的胰岛素依赖型糖尿病（IDDM）的病理生理学和发病机制

• 批准号: 11470175
• 负责人: MATSUURA Nobuo
• 金额: $ 4.8万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470175/
• 关键词: HLA antigen genes; DRβ genes; DQα genes; CTLA-4 gene; NeuroD; BETA2 gene; IDDMK_<1,2>-22; Childhood diabetes; Qoβ gene; 発症感受性遺伝子; HLA抗原遺伝子; 1型糖尿病とQOL; IDDMK1,2-22遺伝子多型; HbAlc値とQOL; BETA2遺伝子; 遺伝子多型; CD30遺伝子; CD30Ligannd遺伝子; 1型糖尿病の多様性; 1型

1. HLA-DR, DQ beta genes and DQ alpha genes analysisWe analyzed HLA antigen genes in 146 patients with IDDM and 97 controls. The patients were divided into three groups, that is, group E, A, and S, depending on the age at onset and clinical course of the disease. We found significantly decreased frequency in DRB1 150X(D) in all diabetic groups, and increased in 0405(S), 0901(V) in groups in A and E.. Moreover, 0802(D) was significantly increased in group A. DQA1(301), DQB1(303), DRB1(901) genotype was found most susceptibility (RR=7.29 , 3.79, 2.82 in groups E, A, E respectively) in Japanese pat.2. CTLA-4 and NeuroD/BETA2 polymorphism associated with Japanese childhood IDDM patients.: We found the significant increase in G/G phenotype, decreas A/A phenotype in group E compared with control. The relationship between HLA DRB1 405 and 901 and CTLA-4 polymorphism was evaluated. Odds ratio(OR) in 0901(+) vs 0901(-) and 0910(+)/CTLA4(G+) vs 0910(-)/CTLA4(G-) as well as 504 was significantly increased in diabetic groups suggested the both genes are additive but independently for the development of IDDM in Japanese children. There was no significant diference in NeuroD/BETA2 polymorphism in Japanese children.3. Idenfication of nonsynonymous polymorphism in the superantigen(SPA)-coding region of IDDMK_<1,2>-22 and association with IDDM: We identified two nonsynony-mous A/G polymorphism at the 339- and 510- in the SPA-coding region of IDDM-K_<1,2>-22 retrovirus. We found significant G/G polymorphism at 510- in group E and G/A phenotype at 339- in group S. Future study will be necessary for conclusions.

1. HLA-DR、DQ β基因和DQ α基因分析对146例IDDM患者和97例对照者进行了HLA抗原基因分析。根据发病年龄和临床病程将患者分为三组，即E组、A组和S组。DRB_1 150 X（D）在糖尿病各组中出现频率明显降低，而0405（S）、0901（V）在A、E组中出现频率明显升高。A组0802（D）明显升高。DQA 1（301）、DQB 1（303）、DRB 1（901）基因型在日本人中的易感性最高（E、A、E组RR分别为7.29、3.79、2.82）。CTLA-4和NeuroD/BETA2多态性与日本儿童IDDM患者相关E组与对照组相比，G/G表型明显增加，A/A表型明显减少。分析HLA DRB 1 405和901与CTLA-4基因多态性的关系。糖尿病组中0901（+）与0901（-）、0910（+）/CTLA 4（G+）与0910（-）/CTLA 4（G-）以及504的比值比（OR）显著增加，表明这两个基因是加和的，但对日本儿童的IDDM的发展是独立的。日本儿童的NeuroD/BETA 2多态性没有显着差异。3. IDDMK_<1，2>-22超抗原（SPA）编码区非同义多态性的鉴定及其与胰岛素依赖型糖尿病的相关性：在IDDM-K_<1，2>-22逆转录病毒SPA编码区339-和510-位点发现两个非同义A/G多态性。E组在510-位点发现G/G多态性，S组在339-位点发现G/A表型。需要进一步研究才能得出结论。

项目成果

Kawasaki E: "Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes"J Clin Endocrinol Metab 86. 86. (2001)

川崎 E：“IA-2 自身抗体表位特异性与日本自身免疫性糖尿病患者发病年龄之间的关联”J Clin Endocrinol Metab 86. 86. (2001)

松浦信夫: "小児1型糖尿病のコントロールと長期予後"小児科. 41(7). 1263-1271 (2000)

Nobuo Matsuura：“儿童 1 型糖尿病的控制和长期预后”《儿科学》41(7) (2000)。

松浦信夫: "小児の糖尿病In糖尿病のマネージメント.チームアプローチと療養指導の実際第3版"医学書院松岡健平,河盛隆造,岩本安彦(編集). 8 (2001)

Nobuo Matsuura：“儿童糖尿病管理。团队方法和治疗指导的实践实践第 3 版”Igakushoin Kenpei Matsuoka、Ryuzo Kawamori、Yasuhiko Iwamoto (eds.) 8 (2001)。

松浦信夫: "小児の糖尿病In糖尿病のマネージメント.チームアプローチと療養指導の実際 第3版"医学書院 松浦健平, 河盛隆造, 岩本安彦(編集). 8 (2001)

Nobuo Matsuura：“儿童糖尿病管理。团队方法和治疗指导实践第 3 版”Igakushoin Kenpei Matsuura、Takazo Kawamori、Yasuhiko Iwamoto (eds.) 8 (2001)。

Kigaki T 他: "Age-associated in crease of fasal corticosterone levels decrease ED2^<hihght>, NF-k,B^<hight activated macrophage>"J Leukoc Biol. 68(1). 21-30 (2000)

Kigaki T 等人：“年龄相关的筋膜皮质酮水平增加会降低 ED2^<高>、NF-k,B^<高活化巨噬细胞>”J Leukoc Biol. 68(1) (2000)。