FAMILIAL EPIDEMIOLOGY--IDDM, ARTHRITIS & THYROID DISEASE

家族流行病学——IDDM、关节炎

• 批准号: 2143903
• 负责人: JANICE S DORMAN
• 金额: $ 32.56万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2143903
• 关键词: alleles; antiviral antibody; autoimmune thyroiditis; diabetes mellitus genetics; disease /disorder proneness /risk; endocrine disorder diagnosis; epidemiology; family genetics; gene expression; genetic polymorphism; histocompatibility typing; human ecology; human genetic material tag; human morbidity; human subject; insulin dependent diabetes mellitus; longitudinal human study; major histocompatibility complex; metabolism disorder diagnosis; musculoskeletal disorder diagnosis; polymerase chain reaction; questionnaires; rheumatoid arthritis; western blottings

Genes in the HLA region of chromosome 6 are known to confer susceptibility to insulin dependent diabetes mellitus (IDDM) and other autoimmune disorders, such as rheumatoid arthritis (RA) and autoimmune thyroid disease (ATD). Specific HLA-DR, DQ and DP locus polymorphisms have been associated with these conditions. However, the causes of the occurrence of more than one autoimmune disease within an individual, or their clustering in families remains unclear. Possible explanations include linkage disequilibrium among HLA susceptibility genes and/or common environmental factors that may be related to their respective etiologies. The increased prevalence of these disorders among women suggest that hormonal factors may also be involved. To investigate the interrelationships between IDDM RA and ATD, we will address two Specific Aims. Aim 1: To estimate the cumulative incidence of RA and ATD in: a) IDDM cases, b) their parents and siblings, and c) the general population of Allegheny County, PA. We hypothesize that the incidence will be highest among the IDDM cases, and lowest in the general, population. Aim 2: To conduct an analytic epidemiologic investigation of genetic/ environmental interactions and the clustering of ATD, RA and IDDM in families. a) We hypothesize that within families, individuals with IDDM, ATD and RA will share HLA haplotypes. Comparison between families will likely reveal unique class II susceptibility alleles for each disorder. b) We hypothesize that after controlling for susceptibility, relatives with IDDM, RA or ATD will have different viral antibody profiles and/or exposure to other environmental risk factors than family members without these diseases. However, common environmental factors may contribute to the occurrence of more than one autoimmune disease within individuals and among relatives. The emerging field of molecular epidemiology has significantly contributed to our knowledge of the genetic/environmental interactions for IDDM within families and across populations. By expanding our research models, and employing state-of-the-art approaches for genetic epidemiologic analyses in families, we will identify candidate HLA susceptibility genes and environmental risk factors that contribute to the occurrence of IDDM, RA and ATD in an individual and their clustering in families. Identification of potential etiologic determinants can lead to the prevention of these autoimmune disorders, which is the ultimate objective of epidemiologic research.

已知6号染色体的HLA区域中的基因赋予 胰岛素依赖型糖尿病（IDDM）和其他 自身免疫性疾病，例如类风湿性关节炎（RA）和自身免疫性疾病， 甲状腺疾病（ATD）。 HLA-DR、DQ和DP位点特异性多态性 与这些疾病有关 然而， 在个体内发生一种以上自身免疫性疾病，或 他们在家庭中的聚集情况仍不清楚。 可能的解释 包括HLA易感基因间连锁不平衡和/或 共同的环境因素，可能与他们各自的 病因学 这些疾病在女性中的发病率增加 这表明荷尔蒙因素也可能参与其中。 探讨 关于IDDM RA和ATD之间的相互关系，我们将讨论两个具体问题， 目标。 目的1：估计RA和ATD在以下人群中的累积发病率：a）IDDM 病例，B）他们的父母和兄弟姐妹，以及c）一般人群 宾夕法尼亚州阿勒格尼县 我们假设，发病率将是最高的 在胰岛素依赖型糖尿病病例中，在一般人群中最低。 目的2：对遗传性/ 环境的相互作用和ATD、RA和IDDM的聚集， 家庭a）我们假设在家庭中，患有IDDM的个体， ATD和RA将共享HLA单倍型。 家庭之间的比较将 可能揭示了每种疾病的独特的II类易感性等位基因。 B）我们假设，在控制了易感性之后， 与IDDM，RA或ATD将有不同的病毒抗体谱和/或 暴露于其他环境危险因素，而不是家庭成员， 这些疾病。 然而，共同的环境因素可能有助于 在个体内发生一种以上的自身免疫性疾病， 亲戚之间。 新兴的分子流行病学领域已经显著地 有助于我们了解基因与环境的相互作用 在家庭和人群中的胰岛素依赖型糖尿病。 通过扩大我们 研究模型，并采用最先进的方法进行遗传 在家庭流行病学分析中，我们将确定候选HLA 易感基因和环境风险因素，有助于 IDDM、RA和ATD在个体中发生及其聚集性 在家庭中。 确定潜在的病因决定因素可能导致 预防这些自身免疫性疾病，这是最终的 流行病学研究的目的。