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.
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.
| Almazar, Ann E; Chang, Joseph Y; Larson, Joseph J et al. (2018) Comparison of Lactase Variant MCM6 -13910 C>T Testing and Self-report of Dairy Sensitivity in Patients With Irritable Bowel Syndrome. J Clin Gastroenterol : |
| Saito, Yuri A (2011) The role of genetics in IBS. Gastroenterol Clin North Am 40:45-67 |
| Saito, Yuri A; Mitra, Nandita; Mayer, Emeran A (2010) Genetic approaches to functional gastrointestinal disorders. Gastroenterology 138:1276-85 |
| Saito, Yuri A; Talley, Nicholas J (2009) AJG series: molecular biology for clinicians. Am J Gastroenterol 104:2583-7 |
| Saito, Yuri A (2008) Genes and irritable bowel syndrome: is there a link? Curr Gastroenterol Rep 10:355-62 |
