MOLECULAR EPIDEMIOLOGY OF IDDM

目前在中国20多个地区建立了胰岛素依赖型糖尿病登记， 根据WHO DiaMond项目提出的标准化方法， 以评估疾病发病率的国内差异。 率似乎 从四川的0.1/10万/年上升到2.0/10万/年 毗邻香港。 如此大的风险差异可能反映了 在中国，种族、文化和基因的多样性是巨大的。 或者，它可能是由于不正确地将儿童分类为 胰岛素-使用NIDDM作为IDDM。 建立基于人口的 低风险异质性国家（如中国）的登记研究， 提供了一个独特的机会，以扩大目前资助的国家卫生研究院的目标， 授予（RO1 DK42316），这是DiaMond分子的基础 流行病学分项目。 拟议的研究将评估 临床特征和潜在遗传（HLA II类等位基因）， 环境（婴儿营养）和免疫（谷氨酸抗体 酸性脱羧酶（GAD）和甲状腺自身抗原）决定簇 15个中国人群中的儿童糖尿病， 具体目标： a. 研究其发病时的临床特征和早期 儿童糖尿病自然史的标准化 为世界卫生组织DiaMond项目建立的胰岛素依赖型糖尿病发病率登记， 1989 - 1993年中国。 B。 为了确定特定的HLA II类等位基因和 基因型与儿童胰岛素依赖型糖尿病和胰岛素治疗的NIDDM相关 使用开发的标准化方法从选定的中国人群中 DiaMond分子流行病学子项目。 C. 为了评估GAD自身抗体的患病率， 过氧化物酶和甲状腺球蛋白在中国胰岛素治疗的NIDDM患者中， 胰岛素依赖型糖尿病病例和无关的非糖尿病对照，并比较这些 结果与白人IDDM病例和非糖尿病患者的结果一致 Allegheny County，PA附近的景点 D. 探讨HLA Ⅱ类基因与自身免疫缺陷的相互作用。 中国人抗GAD、甲状腺过氧化物酶和/或甲状腺球蛋白抗体的研究 胰岛素依赖型糖尿病和胰岛素治疗的非胰岛素依赖型糖尿病患者，并将这些结果与 高加索人胰岛素依赖型糖尿病病例。

IDDM registries are now being established in more than 20 areas of China, according to the standardized methods proposed by the WHO DiaMond Project, to assess the intra-country variation in disease incidence. Rates appear from 0.1/100,000 per year in Sichuan to 2.0/100,000 per year in neighboring Hong Kong. Such a large difference in risk may reflect the tremendous ethnic, cultural and genetic diversity within China. Alternatively, it may result from incorrectly classifying children with insulin-using NIDDM as IDDM. The establishment of population-based registries throughout a low risk heterogenous country, such as China, affords a unique opportunity to extend the aims of a currently funded NIH grant (RO1 DK42316) which is the foundation of the DiaMond Molecular Epidemiology Sub-Project. The proposed research will evaluate the clinical characteristics and potential genetic (HLA class II alleles), environmental (infant nutrition) and immunologic (antibodies to glutamic acid decarboxylase (GAD) and thyroid autoantigens) determinants of childhood diabetes in 15 Chinese populations by addressing the following Specific Aims: A. To examine the clinical characteristics at onset and the early natural history of diabetes in children identified from the standardized IDDM incidence registries being established for the WHO DiaMond Project in China for the years 1989-1993. B. To determine the degree to which specific HLA class II alleles and genotypes are associated with IDDM and insulin-treated NIDDM in children from selected Chinese populations using the standardized methods developed for the DiaMond Molecular Epidemiology Sub-Project. C. To assess the prevalence of auto-antibodies to GAD, thyroid peroxidase and thyroglobulin among Chinese insulin-treated NIDDM patients, IDDM cases and unrelated non-diabetic controls, and to compare these findings with those obtained for Caucasian IDDM cases and non-diabetic controls from Allegheny County, PA. D. To evaluate the interactions between HLA class II alleles and auto- antibodies to GAD, thyroid peroxidase and/or thyroglobulin among Chinese IDDM and insulin-treated NIDDM patients and to compare these findings with those obtained for Caucasian IDDM cases.