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Genetics and Irritable Bowel Syndrome: From Genomics to Intermediate Phenotype and Pharmacogenetics





Dig Dis Sci. 2009 Aug 5. [Epub ahead of print]


Genetics and Irritable Bowel Syndrome: From Genomics to Intermediate Phenotype and Pharmacogenetics.


Camilleri M. Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Charlton 8-110, 200 First Street S.W., Rochester, MN, 55905, USA, This email address is being protected from spambots. You need JavaScript enabled to view it..



PURPOSE: Familial aggregation and sibling pair studies suggest there is a genetic contribution to the development of irritable bowel syndrome (IBS). The aim of this study was to review the evidence of genetics in IBS based on genetic epidemiology, studies of association with intermediate phenotypes and pharmacogenetics.


RESULTS: Genetic association studies with IBS symptom phenotype have generally provided inconsistent results for many candidate genes investigated, such as SLC6A4, GNB3, and IL-10. There have been no genome-wide association studies in IBS to date. Studies of associations of candidate genes with intermediate phenotypes suggest associations with pathophysiological mechanisms of motor and sensory functions; however, these results also require replication. Pharmacogenetics studies illustrate the potential of genetics to impact on response to therapy, as observed with SLC6A4 and responses to the 5-HT3 antagonist alosetron and the 5-HT4 agonist, tegaserod.


CONCLUSIONS: While the heritable component and genetics in the complex disorder of IBS are still poorly understood, studies of the associations of spontaneous genetic variations and altered functions may provide novel insights of the mechanisms contributing to the disease.


PMID: 19655247 [PubMed - as supplied by publisher]










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