EPIDEMIOLOGY AND GENETICS OF IDDM IN FINLAND

芬兰 IDDM 的流行病学和遗传学

• 批准号: 2458750
• 负责人: JAAKKO O TUOMILEHTO
• 金额: $ 20.94万
• 依托单位: NATIONAL INSTITUTE FOR HEALTH & WELFARE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458750
• 关键词: MHC class I antigen; MHC class II antigen; Scandinavian country; adult human (21+); antiviral antibody; child (0-11); diabetes mellitus genetics; diet; disease /disorder proneness /risk; epidemiology; family genetics; genetic markers; genotype; histocompatibility antigens; histocompatibility typing; human birth weight; human subject; immunization; insulin dependent diabetes mellitus; mother /embryo /fetus nutrition; nutrition related tag; patient /disease registry; pregnancy infection; virus diseases

DESCRIPTION: (Adapted from Investigator's Abstract) The main aim of the proposed research is to obtain new information about the etiology of insulin-dependent diabetes mellitus (IDDM) in Finland, where the incidence of IDDM is highest in the world and still increasing. It is assumed that understanding why Finland has the highest incidence rate of IDDM in the world and why the incidence rate is still increasing among Finnish children will lead to the determination of the etiology of IDDM. Since genetic susceptibility to IDDM has been measured by complete HLA genotyping and putative environmental determinants have also been measured, there exists an unique opportunity to estimate the interaction between genetic and environmental factors. The investigators' DiMe study represents the largest family study of IDDM with detailed data on epidemiology, HLA genetics and putative environmental risk factors. During the next three years of support requested, the primary goals will be the analysis of the data collected during the previous years of the study. Data on new cases of childhood IDDM registered in Finland nationwide will be used to determine long-term temporal trends, seasonality, spatial variation, and space-time clustering of IDDM. Also, international comparative analyses will be continued. The genetic family data on HLA-A, C, B, DR, DQ markers and entire HLA haplotypes will be analyzed in detail. Attention will be particularly paid to the haplotype versus single allele effects, and to haplotypes transmitted from a parent with IDDM to the child with IDDM. The role of class I antigens for the risk of IDDM will be evaluated in detail. The case-control studies will be analyzed by addressing the role of various dietary factors, viral infections, and vaccinations in the development of IDDM. In utero effects will be investigated in three ways: comparing the birth weight and length in IDDM cases and controls, comparing the reported diet between mothers of cases and controls, and comparing virus antibody levels in sera between the cases and controls collected during pregnancy. New information will be obtained about the role of genetic and environmental factors in the development of IDDM in 9,463 offspring of 5,261 IDDM patients in a population-based prospective study to determine the reasons for sex-associated effects for the transmission of genetic susceptibility to IDDM.

描述：（根据调查员的摘要改编） 拟议的研究是获取有关病因的新信息 芬兰的胰岛素依赖性糖尿病（IDDM） IDDM的发病率在世界上最高，并且仍在增加。这是 假设理解为什么芬兰的发病率最高 世界上的IDDM以及为什么发病率仍在增加 在芬兰儿童中，将导致病因的确定 IDDM。由于遗传对IDDM的敏感性已通过 完整的HLA基因分型和推定的环境决定因素具有 还测量了 遗传因素与环境因素之间的相互作用。这 研究人员的一角钱研究代表了IDDM的最大家庭研究 有关流行病学，HLA遗传学和推定的详细数据 环境风险因素。在接下来的三年支持中 要求，主要目标是对收集的数据的分析 在研究的前几年。有关新童年案例的数据 在全国芬兰注册的IDDM将用于确定长期 时间趋势，季节性，空间变化和时空 IDDM的聚类。此外，国际比较分析将是 持续。 HLA-A，C，B，DR，DQ标记的遗传家庭数据和 将详细分析整个HLA单倍型。注意将是 特别支付了单倍型与单个等位基因效应，以及 单倍型从带有IDDM的父母传输到具有IDDM的孩子。 I类抗原在IDDM风险中的作用将在 细节。病例对照研究将通过解决 各种饮食因素，病毒感染和疫苗接种的作用 IDDM的发展。在子宫效应中，将在三个 方法：比较IDDM案例和控件中的出生体重和长度， 比较病例和对照母亲之间报告的饮食，以及 比较病例和对照之间血清中的病毒抗体水平 在怀孕期间收集。将获得有关 遗传和环境因素在IDDM发展中的作用 在基于人群的前瞻性中，有5,261名IDDM患者的9,463个后代 研究以确定与性别相关效应的原因 遗传易感性传播到IDDM。

项目成果

Preventing insulin dependent diabetes mellitus: the environmental challenge. Diabetes Epidemiology Research International.

预防胰岛素依赖型糖尿病：环境挑战。

• DOI: 10.1136/bmj.295.6596.479
• 发表时间: 1987
• 期刊: British medical journal (Clinical research ed.)

Empirical Bayes methods for testing associations with large numbers of candidate genes in the presence of environmental risk factors, with applications to HLA associations in IDDM.

经验贝叶斯方法用于在存在环境风险因素的情况下测试与大量候选基因的关联，并应用于 IDDM 中的 HLA 关联。

• DOI: 10.3109/07853899209147843
• 发表时间: 1992
• 期刊: Annals of medicine
• 影响因子: 4.4
• 作者: Thomas,D;Langholz,B;Clayton,D;Pitkäniemi,J;Tuomilehto-Wolf,E;Tuomilehto,J
• 通讯作者: Tuomilehto,J

Natural course of preclinical type 1 diabetes in siblings of affected children.

受影响儿童的兄弟姐妹中临床前 1 型糖尿病的自然病程。

• DOI: 10.1111/j.1651-2227.2003.tb00823.x
• 发表时间: 2003
• 期刊: Acta paediatrica (Oslo, Norway : 1992)
• 作者: Mrena,S;Savola,K;Kulmala,P;Akerblom,HK;Knip,M;ChildhoodDiabetesinFinlandStudyGroup
• 通讯作者: ChildhoodDiabetesinFinlandStudyGroup

Geographical differences within Finland in the frequency of HLA-DQ genotypes associated with type 1 diabetes susceptibility. The Childhood Diabetes in Finland Study Group.

• DOI: 10.1046/j.1365-2370.2000.00223.x
• 发表时间: 2000-08
• 期刊: European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics
• 作者: J. Ilonen;H. Reijonen;A. Green;A. Reunanen;M. Knip;O. Simell;Åkerblom Hk

Effect of polymorphism in the insulin gene region on IDDM susceptibility and insulin secretion. The Childhood Diabetes in Finland (DiMe) Study Group.

胰岛素基因区域多态性对 IDDM 易感性和胰岛素分泌的影响。

• DOI: 10.1111/j.1365-2362.1996.tb02128.x
• 发表时间: 1996
• 期刊: European journal of clinical investigation
• 影响因子: 5.5
• 作者: Halminen,M;Veijola,R;Reijonen,H;Ilonen,J;Akerblom,HK;Knip,M
• 通讯作者: Knip,M