FAMILIAL EPIDEMIOLOGY--IDDM ARTHRITIS & THYROID DISEASE

已知6号染色体上的人类白细胞抗原区域的基因 易患胰岛素依赖型糖尿病(IDDM)和其他 自身免疫性疾病，如类风湿性关节炎(RA)和自身免疫 甲状腺疾病(ATD)。特定的人类白细胞抗原-DR、DQ和DP基因座的多态性 都与这些病症有关。然而，造成这一现象的原因 个体内发生一种以上自身免疫性疾病，或 它们在家庭中的聚集仍不清楚。可能的解释 包括人类白细胞抗原易感基因和/或 可能与它们各自的环境因素有关的共同环境因素 病因学。这些疾病在女性中的患病率增加 这表明荷尔蒙因素也可能参与其中。为了调查 IDDM RA和ATD之间的相互关系，我们将讨论两个具体的 目标。 目的1：评估RA和ATD在a)IDDM中的累积发病率 病例，b)其父母和兄弟姐妹，以及c)一般人口 宾夕法尼亚州阿勒格尼县我们假设发病率最高的是 在IDDM病例中，是一般人群中最低的。 目的2：开展遗传病/艾滋病的分析性流行病学调查 环境交互作用与中国ATD、RA和IDDM的聚集性 家人。A)我们假设，在家庭内，患有IDDM的个人， ATD和RA将共享人类白细胞抗原单倍型。家庭之间的比较将 可能揭示了每个疾病的独特的II类易感等位基因。 B)我们假设，在控制了易感性之后，亲属 对于IDDM，RA或ATD将具有不同的病毒抗体谱和/或 暴露于其他环境风险因素，而不是家庭成员 这些疾病。然而，共同的环境因素可能会导致 在个体内发生一种以上的自身免疫性疾病 在亲戚之间。 分子流行病学的新兴领域已经显著地 有助于我们对遗传/环境相互作用的了解 针对家庭内和跨人群的IDDM。通过扩展我们的 研究模型，并使用最先进的遗传方法 家系流行病学分析，我们将确定候选的人类白细胞抗原 易感基因和环境风险因素 个体中IDDM、RA和ATD的发生及其聚集性 在家庭中。识别潜在的病因决定因素可导致 来预防这些自身免疫性疾病，这是终极 流行病学研究的目的。

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.