GENETIC EPIDEMIOLOGY OF RHEUMATOID ARTHRITIS IN UTAH

风湿性关节炎（RA）是最常见的致残性疾病之一， 影响美国人的疾病 多达两百万的成年人 受影响，这种疾病代表数亿美元， 医疗费用和收入损失。 虽然这种疾病的病因 疾病很复杂，与HLA II类一致相关 抗原（DR）表明这些免疫应答基因可能是 被牵连 此外，最近的DNA研究表明， DR的某些高度多态性区域之间的关联 基因与类风湿性关节炎风险 然而，这些研究还没有 基因连锁研究明确证实，因为 这些后一种研究未能给出一致的结果。 它 这种模糊性很可能是由于基因 对RA的易感性是由HLA和 其他免疫反应基因 这个项目的目的是量化遗传 对RA易感性是由于特异性免疫 反应基因 这一总体目标将通过以下方式实现： 在人口中实现四个相互关联的具体目标 在种族和社会人口上都是同质的。 我们将首先识别和联系每一个确诊的RA病例 居住在研究区域（犹他州及周边地区）。 第二、 这一人群中疾病的家族聚集程度 将通过问卷调查和随访相结合进行评估 第三，我们将进行匹配的病例对照 对60名多重先证者（有受影响亲属的患者）的研究， 120例单纯先证者（无受影响亲属的患者）和120例 随机控制，以确定是否人口的疾病风险 是由于不同免疫反应基因之间的相互作用。 该分析将包括对DNA序列的评估 DR区域的差异。 第四，我们将进行详细的 临床、血清学和遗传学（DNA和HLA）评估 代表这些人家属的大约1 140人 60名先证者，以确定 家系内的免疫应答基因影响家族性免疫应答。 RA的分布

Rheumatoid arthritis (RA) is one of the most common crippling diseases to affect Americans. With up to two million adults affected, this disease represents hundreds of millions of dollars of medical expenses and lost income. While the etiology of this disease is complex, the consistent association with HLA class II antigens (DR) indicates that these immune response genes are likely to be implicated. In addition, recent DNA studies suggest an association between certain highly polymorphic regions of the DR gene and risk of RA. However, these association studies have yet to be unambiguously confirmed by genetic linkage studies, since these latter studies have failed to give consistent results. It is very likely that this ambiguity is due to the fact that genetic susceptibility to RA results from an interaction between HLA and other immune response genes. This project is designed to quantify the extent to which genetic susceptibility to RA is due to interaction between specific immune response genes. This overall objective will be achieved by carrying out four interrelated specific aims within a population that is both ethnically and sociodemographically homogeneous. We will first identify and contact every diagnosed case of RA resident in the study area (Utah and surrounding regions). Second, the extent of familial aggregation of disease in this population will be assessed by a combination of questionnaires and followup clinical exam. Third, we will carry out a matched case-control study of 60 multiplex probands (patients with affected relatives), 120 simplex probands (patients without affected relatives) and 120 random controls to determine whether the population risk of disease is due to interaction between different immune response genes. This analysis will include an evaluation of DNA sequence differences at the DR region. Fourth, we will carry out a detailed clinical, serological and genetic (DNA and HLA) evaluation of approximately 1,140 individuals representing the families of these 60 probands to determine the extent to which interaction between immune response genes within pedigrees influences the familial distribution of RA.