MOLECULAR EPIDEMIOLOGY OF IDDM

IDDM 的分子流行病学

• 批准号: 2150405
• 负责人: JANICE S DORMAN
• 金额: $ 25.22万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2150405
• 关键词: China; MHC class II antigen; SDS polyacrylamide gel electrophoresis; autoantibody; blood chemistry; caucasian American; child (0-11); developmental nutrition; diabetes mellitus genetics; enzyme activity; epidemiology; genetic markers; genotype; glutamate decarboxylase; human genetic material tag; human subject; immunoprecipitation; insulin dependent diabetes mellitus; pathologic process; patient /disease registry; peroxidases; protein sequence; racial /ethnic difference; thyroglobulin; western blottings

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.

目前正在中国的20多个地区建立IDDM登记处， 根据世卫组织钻石项目提出的标准化方法， 评估疾病发病率的国家内差异。出现费率 四川从每年0.1/10万下降到2000年的2.0/10万 邻近的香港。如此大的风险差异可能反映了 中国体内存在着巨大的民族、文化和遗传多样性。 或者，它可能是由于错误地将儿童归类为 胰岛素--使用NIDDM作为IDDM。建立以人口为基础的 低风险异质国家的登记，如中国， 提供了一个独特的机会来延长目前资助的NIH的目标 Grant(RO1 DK42316)，这是钻石分子的基础 流行病学子项目。拟议的研究将评估 临床特征和潜在的遗传(人类白细胞抗原II类等位基因) 环境(婴儿营养)和免疫学(谷氨酸抗体 酸性脱羧酶(GAD)和甲状腺自身抗原)决定因素 通过解决以下问题在15个中国人中发现儿童糖尿病 具体目标： 检查发病初期和早期的临床特征。 标准化儿童糖尿病自然病史的鉴定 年正在为世卫组织钻石项目建立IDDM发病登记 1989年至1993年的中国任期。 B.确定特定的人类白细胞抗原II类等位基因和 儿童IDDM和胰岛素治疗的NIDDM与基因分型有关 使用开发的标准化方法从选定的中国人群中 钻石分子流行病学子项目。 C.评估GAD、甲状腺自身抗体的流行率 中国胰岛素治疗的非胰岛素依赖型糖尿病患者的过氧化物酶和甲状腺球蛋白 IDDM病例和不相关的非糖尿病对照组，并将它们进行比较 高加索人IDDM病例和非糖尿病患者的研究结果 来自宾夕法尼亚州阿勒格尼县的控制组。 D.评估人类白细胞抗原II类等位基因与自身免疫性疾病的相互作用 中国人GAD、甲状腺过氧化物酶和/或甲状腺球蛋白抗体的调查 IDDM和胰岛素治疗的NIDDM患者，并将这些发现与 针对高加索人IDDM病例获得的数据。