Immune/Inflammation Genomics and the Risk of SLE and CHD

6.项目摘要/摘要 系统性红斑狼疮(SLE)是一种典型的全身性炎症性自身免疫病 主要影响更年轻的绝经前妇女。系统性红斑狼疮患者发生冠状动脉热病的风险 女性的比例高达普通人群的50倍。传统的风险因素不足以 解释系统性红斑狼疮患者的早发冠心病。这表明SLE患者有一些独特的东西 使他们面临极高的冠心病风险。炎症和免疫因素可能起着重要的作用。 在此病因学中扮演的角色。系统性红斑狼疮是一种复杂的多因素疾病，可能涉及几个 遗传和环境因素。遗传因素在系统性红斑狼疮的病因中有很强的参与 S在20-40岁之间的家族风险估计和高达66%的遗传度证明了这一点。强大的生物性 免疫和炎症反应参与SLE病因的证据与 系统性红斑狼疮具有强大的遗传基础的证据为研究遗传变异的作用提供了强有力的理论基础。 参与免疫/炎症途径的基因与系统性红斑狼疮和系统性红斑狼疮的冠心病风险有关。在这 应用：我们打算检验一种假设，即参与免疫/炎症的基因遗传变异 它们之间的通路和相互作用与SLE风险和CHD风险均相关。我们将使用 Affymetrix免疫和炎症9K SNP试剂盒，在大约1,000个SNP中包含约9,200个SNP 基因，包括基于HapMap的标签SNPs(频率为5%)和另外773个已验证的非同义词 SNPs。在确定重要的SNPs后，我们将在相关基因/区域中筛选额外的SNPs，以便 找到可能的功能变体。作为这些分析的结果，我们应该能够确定 同时，共同变异在大量生物相关免疫/炎症中的作用 SLE中SLE风险和CHD风险的基因。

6. Project Summary / Abstract Systemic lupus erythematosus (SLE) is the prototypic systemic inflammatory autoimmune disease that affects predominantly younger premenopausal women. The risk of coronary heat disease (CHD) in SLE women is up to 50 times higher than in the general population. The conventional risk factors are insufficient to explain premature CHD in SLE patients. This indicates that there is something unique about SLE patients that render them at extremely high risk for CHD. It is likely that inflammatory and immune factors play an important role in this etiology. SLE is a complex and multifactorial disease with the possible involvement of several genetic and environmental factors. The strong involvement of genetic factors in the etiology of SLE is evidenced by familial risk estimates of ¿s between 20-40 and heritability of up to 66%. The strong biological evidence of the involvement of immune and inflammatory responses in the etiology of SLE couple with the evidence that SLE has a strong genetic basis provide strong rationale to examine the role of genetic variation in genes involved in immune/inflammation pathways in relation to SLE and the risk of CHD in SLE. In this application we intend to test the hypothesis that genetic variation in genes involved in immune/inflammation pathways and interactions among them are associated with both SLE risk and CHD risk in SLE. We will use the Affymetrix Immune and Inflammatory 9K SNP kit that contains about 9,200 SNPs in approximately 1,000 genes, including HapMap-based tagSNPs (frequency >5%) and additional 773 validated non-synonymous SNPs. After identifying significant SNPs, we will screen additional SNPs in relevant genes/ regions in order to locate putative functional variants. As a result of these analyses, we should be able to determine simultaneously the role of common variation in a large number of biologically relevant immune/inflammation genes that contribute to SLE risk and CHD risk in SLE.