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Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response

The Pharmacogenomics Journal volume 3, pages 64–66 (2003)Cite this article

The most significant medical advances have unmistakable genetic components,1 ranging from disease susceptibility to diversity in therapeutic response. Modern medicine's genetic emphasis is evident through clinicians' attempts to translate particular genotypes into clinical phenotypes, ever hopeful that in the near future selection of therapy will be based on a patient's genetic background. The basis of this new correlative science is predicated on the idea that genetic heterogeneity may allow physicians to tailor individual therapy, and therefore maximize clinical benefits while minimizing toxicity and cost. The human genome is 99.9% identical in all individuals. Individual differences are determined by only 0.1% of the genome.2,3 This very small fraction of the genome, which expresses polymorphisms, is responsible for disease susceptibility and therapeutic response. These genetic polymorphisms may influence clinical phenotypes. Camilleri et al4 propose that genetic polymorphisms at the serotonin-transporter (SERT) promoter influence response to a serotonin (5-HT3) antagonist in diarrhea predominant irritable bowel syndrome (D-IBS) patients and may affect the risk-benefit ratio with this class of compounds.

IBS is a constellation of symptoms, varying from abdominal pain, discomfort, bloating, dyspepsia, to altered bowel habits. IBS is a leading cause of lost productivity at work. These symptoms affect upwards of 15% of the adult population, and many of these patients are women.5 D-IBS is characterized by accelerated small bowel and/or colonic transit as well as visceral and specifically rectal hypersensitivity. Neural influences on gut motility provide a mechanism by which an individual's neurotransmittters such as serotonin might influence gut function in D-IBS.

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  1. Division of Gastroenterology and Hepatology, The Weill Medical College of Cornell University, The New York Presbyterian Hospital, New York, USA

    E Scherl & C L Frissora

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  1. E Scherl
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  2. C L Frissora
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Correspondence to C L Frissora.

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Scherl, E., Frissora, C. Irritable bowel syndrome genophenomics: correlation of serotonin-transporter polymorphisms and alosetron response. Pharmacogenomics J 3, 64–66 (2003). https://doi.org/10.1038/sj.tpj.6500163

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