SLE and UC Study

SLE 和 UC 研究

• 批准号: 7032101
• 负责人: John D. Rioux
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032101
• 关键词: African Caribbean; clinical research; cooperative study; gene interaction; genetic mapping; genetic susceptibility; human genetic material tag; human subject; major histocompatibility complex; natural killer cells; single nucleotide polymorphism; systemic lupus erythematosus; ulcerative colitis

The long term objectives of this application are to obtain a precise understanding of how genetic variants located in the major histocompatibility complex (MHC) can influence an individual's risk to developing ulcerative colitis (UC) or systemic lupus erythematosus (SLE); two chronic inflammatory diseases. The MHC region is a large region on chromosome 6p that contains approximately 150 genes; many of which have important roles in the human immune system, including the human leukocyte antigen (HLA) genes. Such an understanding will improve our knowledge of the mechanisms that lead to these and other inflammatory diseases and may provide important molecular markers of disease. Previous studies have been limited by the number of samples examined and by the availability of appropriate genetics tools. The current proposal takes advantage of recent advances in our understanding of the patterns of genetic variation in the human genome. Furthermore, this proposal will take advantage of a very high density map of the genetic variation in the MHC region (approximately 1 SNP per 500-1000 bp). This map will enable the selection of an informative screening set of SNPs to perform a powerful association mapping study. This screening set of SNPs will be applied to large well-characterized UC and SLE patient cohorts. The identical screening set of SNPs will also be applied to multiple other autoimmune diseases. Comprehensive association mapping of the regions identified in this screen will be pursued. In addition, recent work has demonstrated the importance of functionally relevant combinations of alleles of the killer immunoglobulin-like receptor (KIR) and HLA genes in influencing the human immune response. It is believed that this influence of allelic combinations acts in part at the level of the NK cell. Given the emerging importance of NK cells in SLE, we will specifically test for association between KIR/HLA combinations and susceptibility to SLE. This work promises to have an impact on public health by identifying the genetic factors that influence an individual's susceptibility to ulcerative colitis or systemic lupus erythematosus, two chronic inflammatory diseases. This work will also provide important molecular markers of diseases that may be useful in clinical management of these debilitating diseases.

这项应用的长期目标是精确了解位于主要组织相容性复合体（MHC）中的遗传变异如何影响个体发生溃疡性结肠炎（UC）或系统性红斑狼疮（SLE）的风险；两种慢性炎性疾病。MHC区域是6p染色体上的一个大区域，包含大约150个基因；其中许多在人体免疫系统中起着重要作用，包括人类白细胞抗原（HLA）基因。这样的理解将提高我们对导致这些和其他炎症性疾病的机制的认识