GENETIC LINKAGE IN LUPUS

狼疮的遗传连锁

• 批准号: 6349781
• 负责人: John Barker Harley
• 金额: $ 84.57万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349781
• 关键词: Epstein Barr virus; Herpesviridae disease; antiviral antibody; autoantibody; autoantigens; autoimmunity; clinical research; disease /disorder proneness /risk; family genetics; genetic markers; genetic polymorphism; human subject; linkage mapping; phenotype; serology /serodiagnosis; systemic lupus erythematosus; virus infection mechanism

The genetic basis of systemic lupus erythematosis has been pursued using the last five years of funding from this grant (AR24717-07 to -11) to help perform and evaluate a genome scan in lupus. These results considered with those of our closest competitor show 26 possible genetic linkages with 11 of these having some support for linkage from both studies. In addition, we confirm evidence supporting the presence of linkage at D1s229. Other work has advanced Epstein-Barr virus as a possible etiologic agent in lupus. Data show association, are consistent with Epstein-Barr virus infection preceding lupus onset, and advance a plausible mechanism for lupus autoimmunity in some patients. Virus exposure data and differences between the anti-viral immune responses of lupus patients and normal are amenable to genetic analysis in our pedigrees. In aggregate, we have 2109 pedigrees multiplex for lupus containing 1227 subjects (275 affecteds & 752 unaffecteds). We hope to continue our work by pursuing the following specific aims: 1. Enlarge the pedigree collection; 2. Establish linkage using: A. Lupus (by revised ACR criteria), B. An environmental factor and intermediate phenotypes: i. Lupus and Epstein-Barr virus infection, ii. Anti-peptide antibodies against Epstein-Barr virus (& against lupus autoantigens), iii. Anti-Ro and anti-nRNP autoantibody responses, and C. Multi-locus effects, and 3. Reduce linkage intervals and evaluate candidate genes. Hopefully, results from this resubmitted project will help elucidate the complex genetics of lupus.

系统性红斑狼疮的遗传基础一直在使用过去五年的资助（AR 24717 -07至-11），以帮助执行和评估狼疮的基因组扫描。这些结果与我们最接近的竞争对手的结果一起考虑，显示出26种可能的遗传连锁，其中11种在两项研究中都有一定的连锁支持。此外，我们证实了证据支持存在的联系在D1 s229。其他的工作已经将EB病毒作为狼疮的可能病原体。数据显示相关性，与狼疮发作前的EB病毒感染一致，并提出了一些患者狼疮自身免疫的合理机制。病毒暴露数据和狼疮患者与正常人抗病毒免疫反应之间的差异适用于我们家系的遗传分析。总的来说，我们有2109个狼疮多重家系，包含1227个受试者（275个受累者和752个未受累者）。我们希望通过追求以下具体目标来继续我们的工作：1.扩大系谱收藏; 2.建立链接使用：A.狼疮（根据修订的ACR标准），B。环境因素和中间表型：i.狼疮和EB病毒感染，ii.针对EB病毒（和针对狼疮自身抗原）的抗肽抗体，iii.抗Ro和抗nRNP自身抗体应答，以及C.多位点效应; 3. 减少连锁间隔并评估候选基因。希望这个重新提交的项目的结果将有助于阐明狼疮的复杂遗传学。