Analysis of Genetic Susceptibility to Anterior Uveitis

前葡萄膜炎遗传易感性分析

• 批准号: 6591173
• 负责人: TAMMY M MARTIN
• 金额: $ 19.46万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6591173
• 关键词: eye disorder diagnosis; family genetics; gene expression; gene mutation; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genotype; human genetic material tag; human subject; iridocyclitis; linkage mapping; major histocompatibility complex; patient oriented research; questionnaires

DESCRIPTION (provided by applicant): Acute anterior uveitis (AAU) describes an inflammation of the anterior uveal tract of the eye and is diagnosed by the presence of infiltrating leukocytes in the anterior chamber. For many patients, uveitis is a recurrent condition that may not respond well to the treatments available. A well-defined form of uveitis is anterior, acute (as opposed to chronic), sudden onset, recurrent and unilateral. This is the most common form of uveitis. In many, the disease is familial and is often associated with the marker, HLA-B27. We propose to identify uveitis susceptibility genes by conducting microsatellite genetic analyses in well-defined pedigrees. First, we propose to identify families with two or more members afflicted with AAU. This will be accomplished through a variety of sources including the North American Spondylitis Consortium, the uveitis clinic at Oregon Health Science University, various ophthalmologists around the U.S. who are members of the American Uveitis Society and/or Proctor Fellows, and the Spondylitis Association of America. We anticipate the enrollment of 200 multiplex AAU families. Second, the AAU phenotype of each study participant will be validated and blood will be drawn as a source of genomic DNA. Third, the Major Histocompatibility Complex haplotypes of each participant will be determined so as to analyze the contribution of these genes to the disease. Fourth, whole genome scan will be conducted and examined by sib pair analyses to identify regions of interest in the genome. Fifth, fine-scale mapping studies within the regions of interest will be done to identify candidate genes. These regions of interest will be those i) implicated in the susceptibility to related diseases, including ankylosing spondylitis, and ii) identified from our genome-wide scan. Sixth, we will determine the prevalence of candidate gene mutations among families with AAU. Seventh, we will enroll 100 patients with non-familial AAU in an association study and examine known gene polymorphisms implicated in AAU and other inflammatory diseases. This association study will also include patients with other forms of uveitis. Our goal of identifying genes (in addition to HLA-B27) that contribute to AAU susceptibility could have important therapeutic and preventative implications.

描述（由申请人提供）：急性前葡萄膜炎（AAU）描述 眼睛前尿路的炎症，并被诊断 前腔中存在浸润的白细胞。对于许多患者， 葡萄膜炎是一种反复发生的疾病，可能对治疗的反应不佳 可用的。明确的葡萄膜炎形式是前方的，急性（与 慢性），突然发作，复发和单侧。这是最常见的形式 葡萄膜炎。在许多情况下，该疾病是家族性的，通常与 标记，HLA-B27。我们建议通过 在定义明确的血统中进行微卫星遗传分析。 首先，我们建议确定患有两个或更多成员的家庭 AAU。这将通过包括北方在内的各种来源来实现 俄勒冈州健康科学的葡萄膜炎诊所美国脊柱炎财团 大学，美国各地的各种眼科医生 美国葡萄膜炎协会和/或普罗克特研究员以及脊柱炎 美国协会。我们预计将有200个多重AAU的入学 家庭。其次，每个研究参与者的AAU表型将得到验证 血液将作为基因组DNA的来源。第三，专业 将确定每个参与者的组织相容性复合型单倍型 为了分析这些基因对疾病的贡献。第四，整体 基因组扫描将通过SIB对分析进行并检查 基因组感兴趣的区域。第五，精细的映射研究 感兴趣的区域将进行确定候选基因。这些区域 兴趣将是I）与对相关疾病的敏感性有关的i） 包括脊椎炎，以及从我们的全基因组扫描中鉴定出来的II）。 第六，我们将确定候选基因突变的患病率 有AAU的家庭。第七，我们将招募100名非家庭AAU患者 在协会研究中，并检查了与AAU有关的已知基因多态性 和其他炎症性疾病。该协会研究还将包括 患有其他形式的葡萄膜炎的患者。我们识别基因的目标（在 除了HLA-B27）有助于AAU易感性可能具有重要的 治疗和预防性的影响。