Investigating of Candidate Genes in SLE

系统性红斑狼疮(SLE)是一种遗传性和遗传性的复杂自身免疫性疾病。 仍未完全确定的环境风险因素。免疫调节的变化 通路被认为在疾病的发病机制中起着重要作用，数百项研究 研究了潜在候选基因在不同种族和大小的人群中的作用， 结果往往相互矛盾。免疫调节途径中的数百个其他候选基因 似乎也适合研究，特别是因为还没有关于它们在 SLE。这个可行性项目的目的是筛选出我们一长串有趣的候选者名单 在未来的大型提案中有几个值得专门研究的基因。在具体目标1中，我们将测试一个 由400名系统性红斑狼疮患者和400名匹配对照组成的欧美样本队列 通过SNP-Gen Core在我们候选列表中的基因中选择了384个SNPs。我们有400个 非洲裔美国人病例和手头近300个匹配的对照，为了具体目标2，我们将 招募更多的非裔美国人患者和对照在同一阵列上进行测试。对于特定的 目标3我们利用这些欧洲裔美国人和非洲裔美国人队列的结果来选择 有希望进行进一步研究的基因，并在包含这两个基因的确认上进行测试 来自欧洲裔美国人、非洲裔美国人和西班牙裔美国人的基于家庭的病例对照样本 家人。对于在这一阶段确认的关联，特定目标4将检查基因以 在关联的SNP不编码结构SNP的情况下查找功能多态性 变种或已知的监管部位。这些结果将使无可争议的基因鉴定成为可能 SLE的危险因素。与系统性红斑狼疮相关的功能多态性的发现将是 更广泛的结构/功能研究的完美跳板，以及 随后的资金申请。

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with both genetic and environmental risk factors that remain incompletely defined. Alterations in the immune regulatory pathways are believed to play an important role in disease pathogenesis, and hundreds of studies have examined the role of potential candidate genes in populations of varying ethnicity and size, often with conflicting results. Hundreds of other candidate genes in immune regulatory pathways appear ripe for study as well, especially since no results have been published regarding their role in SLE. The purpose of this feasibility project is to winnow down our long list of interesting candidates to a few genes worthy of dedicated study in future large proposals. In Specific Aim 1, we will test a cohort of European-American samples consisting of 400 SLE cases and 400 matched controls at 384 SNPs chosen within genes in our candidate lists through the SNP-Gen Core. We have 400 African-American cases and nearly 300 matched controls on hand, and for Specific Aim 2 we will recruit additional African-American patients and controls for testing on the same array. For Specific Aim 3 we utilize on the results of these European-American and African-American cohorts to select genes with promising associations for further study and test them on a confirmation containing both family-based and case-control samples from European-American, African-American, and Hispanic families. For those associations confirmed in this phase, Specific Aim 4 will examine the genes to find functional polymorphisms in cases where the associated SNP does not encode a structural variant or a known regulatory site. These results will enable identification of indisputable genetic risk factors for SLE. The finding of a functional polymorphism associated with SLE would be the perfect springboard for more extensive structure/function studies and the starting point of subsequent applications for funding.