Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome

Michael Camilleri, Elena Atanasova, Paula J. Carlson, Umraan Ahmad, Kim, Blanca E. Viramontes, Sanna McKinzie, Raul Urrutia

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229 Scopus citations

Abstract

Background & Aims: A serotonin (5-HT)3 receptor antagonist relieves symptoms in women with diarrhea-predominant irritable bowel syndrome (D-IBS). 5-HT undergoes reuptake by a transporter protein (SERT). Polymorphisms in the promoter for synthesis of SERT (SERT-P) influence response to serotonergic medications in depression. Our hypothesis is that polymorphisms of the promoter region for the SERT influence colonic transit in response to treatment with alosetron in D-IBS. Methods: Thirty patients (15 men, 15 women) with D-IBS received 1 mg twice a day alosetron for 6 weeks; colonic transit was measured by scintigraphy at baseline and at the end of treatment. Twenty-three patients consented to provide blood DNA samples. Long, short, and heterozygous SERT polymorphisms were identified by polymerase chain reaction-based restriction fragment length polymorphisms and confirmed by direct sequencing. We sought pharmacogenomic association of long, short, and heterozygote polymorphisms with a change in colonic transit and with an a prioridefined, clinically meaningful change in transit at 24 hours (>1.1 colonic regions). Results: SERT polymorphisms tended to be associated with colonic transit response (P = 0.075); there was a greater response in those with long homozygous than heterozygous polymorphisms (P = 0.039). Slowing of transit by >1.1 colonic region was observed in 9 women and 3 men and was more frequent in long homozygous than heterozygous patients (P = 0.024). Age, gender, and duration of IBS were not significantly different in the 3 groups. Conclusions: Genetic polymorphisms at the SERT promoter influence response to a 5-HT3 antagonist in D-IBS and may influence benefit-risk ratio with this class of compounds.

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalGastroenterology
Volume123
Issue number2
DOIs
StatePublished - Aug 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Camilleri, M., Atanasova, E., Carlson, P. J., Ahmad, U., Kim, Viramontes, B. E., McKinzie, S., & Urrutia, R. (2002). Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome. Gastroenterology, 123(2), 425-432. https://doi.org/10.1053/gast.2002.34780