A candidate gene association study of irritable bowel syndrome

描述(由申请人提供)： 肠易激综合征(IBS)是一种常见的慢性疾病，会导致高昂的医疗费用、残疾和生活质量下降。Yuri Ann Saito-Loftus博士的长期目标是了解这种疾病的病理生理学，以便发现更好的测试和治疗方法。她的K23导师以患者为导向的研究职业发展奖利用一项家庭病例对照研究设计来收集证据，以确定IBS是否有遗传基础。这项申请建议通过使用从K23研究收集的数据和DNA来实现两个额外的特定目标来补充K23研究。由于5-羟色胺和5-羟色胺相关蛋白参与了IBS的病理生理过程，我们建议进行一项基于途径的候选基因关联研究，以确定编码5-羟色胺相关分子的基因变异是否与IBS相关。利用我们研究所的高通量基因分型资源，将对645例患者和323名对照的22个5-羟色胺途径基因的384个连锁不平衡(LD)标记SNPs进行基因分型，并将分析IBS亚组，以确定这种临床异质性疾病是否存在遗传异质性的证据。到目前为止，还没有进行过这种类型和规模的候选基因关联研究，可以为未来的研究提供特定的基因和分子靶点。与公共卫生相关的肠易激综合征(IBS)是一种常见的慢性疾病，由于潜在的机制尚不清楚，它会导致高昂的医疗费用和残疾。这项研究的广泛目标是为未来的研究确定特定的基因和分子靶点，以便开发更好的测试和治疗方法。通过这项研究，我们建议使用收集的DNA和我们机构的高通量基因分型资源来研究基因组，以确定是否存在可能包含导致IBS的遗传变异或突变的区域。

DESCRIPTION (provided by applicant): Irritable bowel syndrome (IBS) is a common chronic disorder that results in high health care expenditures, disability, and decreased quality of life. Dr. Yuri Ann Saito-Loftus' long term objective is to understand the pathophysiology of this disorder so that better tests and treatments may be discovered. Her K23 Mentored Patient-Oriented Research Career Development Award utilizes a family case-control study design to collect evidence for whether there is a genetic basis for IBS. This application proposes to supplement the K23 study by accomplishing two additional specific aims using data and DNA collected from the K23 study. Because serotonin and serotonin-related proteins have been implicated in the pathophysiology of IBS, we propose performing a pathway-based candidate-gene association study to determine whether genetic variants in genes encoding serotonin-related molecules are associated with IBS. Using our institution's high-throughput genotyping resources, 384 linkage disequilibrium (LD) tag SNPs in 22 serotonin pathway genes will be genotyped in 645 cases and 323 controls, and IBS subgroups will be analyzed to determine whether there is evidence for genetic heterogeneity for this clinically heterogeneous disorder. A candidate gene association study of this type and scale has not been performed to date and could provide specific genes and molecular targets for future study. PUBLIC HEALTH RELEVANCE Irritable bowel syndrome (IBS) is a common chronic disorder that results in high health care expenditures and disability because the underlying mechanism is unknown. The broad objective of this study is to identify specific genes and molecular targets for future study so that better tests and treatments may be developed. With this study, we propose using collected DNA and our institution's high-throughput genotyping resource to study the genome to determine whether there are regions that may contain genetic variants or mutations responsible for IBS.