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Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1.
- Source :
- Neurogastroenterology & Motility; Jan2015, Vol. 27 Issue 1, p82-91, 10p
- Publication Year :
- 2015
-
Abstract
- Background Serotonin type 3 receptor (5- HT<subscript>3</subscript>R) antagonists are potentially useful therapeutic agents for diarrhea-predominant irritable bowel syndrome ( IBS-D). To identify biomarkers predicting effectiveness of the 5- HT<subscript>3</subscript>R antagonist (ramosetron) in IBS-D. Methods Irritable bowel syndrome-D Japanese subjects received 2.5 or 5 μg of ramosetron once daily for 4 weeks. Colonic mucosal S100A and tryptophan hydroxylase ( TPH) mRNA expression levels were measured before treatment. Genomic DNA was extracted from blood and polymorphisms of TPH1 and TPH2 were analyzed. Key Results Forty-two patients (27 men and 15 women, mean age 42 years) with IBS-D were included for analysis. Improvement of IBS symptoms was seen in 26 (61.9%). Baseline S100A10 ( p = 0.02) and TPH1 ( p = 0.02) expression were significantly higher in the ramosetron responders than in the non-responders. The frequencies of the TPH1 rs4537731G allele in linkage disequilibrium with the TPH1 rs7130929 T allele (11.5% vs 50%, p = 0.003; OR: 12; 95% CI: 2.1-69) along with TPH1 rs211105 C allele (3.8% vs 43.8%, p = 0.0003; OR: 19; 95% CI: 2.1-181) were significantly lower in the responders than in the non-responders. The mean scores of diarrhea at baseline were significantly higher (5.2 vs 3.7, p = 0.005) in patients with TPH1 rs211105 T/T than those with the G allele. Conclusions & Inferences TPH1 gene polymorphisms and S100A10 expression, which correlate with 5- HT signaling were associated with ramosetron effectiveness in IBS-D, and may possibly lead to prospective identification of the resistance to treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 13501925
- Volume :
- 27
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Neurogastroenterology & Motility
- Publication Type :
- Academic Journal
- Accession number :
- 100178366
- Full Text :
- https://doi.org/10.1111/nmo.12473