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Gastroenterology. 2002 Aug;123(2):425-32.

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

Author information

1
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Foundation, Rochester, Minnesota 55905, USA. camilleri.michael@mayo.edu

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 priori-defined, 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-HT(3) antagonist in D-IBS and may influence benefit-risk ratio with this class of compounds.

PMID:
12145795
DOI:
10.1053/gast.2002.34780
[Indexed for MEDLINE]

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