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Candidate Genes and Sensory Functions in Health and Irritable Bowel Syndrome





Am J Physiol Gastrointest Liver Physiol. 2008 May 29. [Epub ahead of print]


Candidate Genes and Sensory Functions in Health and Irritable Bowel Syndrome.


Camilleri M, Busciglio I, Carlson P, McKinzie S, Burton D, Baxter K, Ryks M, Zinsmeister AR. Mayo Clinic.



Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (GI) function; these effects are mediated through G protein transduction. Candidate genetic variations in ADR-SER were significantly associated with somatic scores in IBS and gastric emptying, but not small bowel or colonic transit. Our aim was to assess whether candidate ADR-SER genes are associated with motor and sensory GI functions in IBS and subgroups based on bowel dysfunction. In 122 IBS patients and 39 healthy controls, we assessed gastrointestinal, somatic symptoms and effect by validated questionnaires. We measured: gastric volume (GV); maximum tolerated volume [MTV]); rectal compliance, sensation thresholds and ratings, and genetic variations: alpha2A (C-1291G), alpha2C (Del 332-325), GNbeta3 (C825T) and 5-HTTLPR. Demographics and genotype distributions were similar in IBS patients subgrouped on bowel function. There were significant associations between 5-HTTLPR SS genotype and absence of IBS symptoms and between 5-HTTLPR LS/SS genotype and increased rectal compliance and increased pain ratings, particularly at 12 and 24 mmHg distensions. GNbeta3 was associated only with fasting GV; we did not detect associations between alpha2A genotype and gastrointestinal sensory or motor functions tested. We concluded that 5-HTTLPR LS/SS genotype is associated with both increased pain sensation and increased rectal compliance though the latter effect is unlikely to contribute to increased pain sensation ratings with LS/SS genotype. The data suggest the hypotheses that the endophenotype of visceral hypersensitivity in IBS may be partly related to genetic factors and the association of GNbeta3 with fasting GV may explain, in part, the reported association of GNbeta3 with dyspepsia. Key words: adrenergic, serotonergic, GN3, SLC6A4.









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