Clinical–Alimentary TractSerotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome☆,☆☆
Section snippets
Patient population and timing of physiological studies
Thirty European American patients with IBS associated with diarrhea and fulfilling Rome I criteria25 were included in this study. Gastrointestinal and colonic transit measurements were performed during the baseline period and during the last week of a 6-week trial with alosetron 1 mg twice a day. Detailed results of the transit measurements and adverse effects during the pharmacodynamic trial are published elsewhere.15 The sample size of 30 patients was selected based on an anticipated change
Patients and duration of IBS
Demographic data of the 30 white participants, 15 women and 15 men, are as follows: mean age 43.2 ± 3 years (women, 46 ± 4 years; men, 40 ± 4 years); mean duration of IBS 11.2 ± 2.0 years (women, 9.2 ± 2.3 years; men, 13.1 ± 3.2 years).
Effect of alosetron on colonic transit
The colonic geometric center at 24 hours was significantly lower (suggesting slower overall colonic transit) following treatment with alosetron compared with baseline.15 The change in overall colonic transit was significantly greater in women compared with men
Discussion
Our study demonstrates for the first time that the homozygous long polymorphism of the SERT-P is associated with a greater biological response and the likelihood of a clinically meaningful effect of alosetron, compared with the response in heterozygotes. These data are consistent with the study by Lesch et al.23 in human lymphoblasts expressing the 3 common genotypes at this locus, “ll,” “ls,” and “ss,” and the observation that there was higher serotonin transport and higher messenger RNA
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Address requests for reprints to: Michael Camilleri, M.D., Mayo Clinic, Charlton 7-154, 200 First Street S.W., Rochester, Minnesota 55905. e-mail: [email protected]; fax: (507) 255-5720.
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Supported in part by General Clinical Research Center grant RR00585, grants R01 DK54681 and K24 DK02638 (to M.C.), and grants RO1 DK52913 and DK56220 (to R.U.) from the National Institutes of Health. The transit measurements in this study were supported by a grant from Glaxo Wellcome.