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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 TPH

dc.contributor.authorShiotani, A.en_US
dc.contributor.authorKusunoki, H.en_US
dc.contributor.authorIshii, M.en_US
dc.contributor.authorImamura, H.en_US
dc.contributor.authorManabe, N.en_US
dc.contributor.authorKamada, T.en_US
dc.contributor.authorHata, J.en_US
dc.contributor.authorMerchant, J. L.en_US
dc.contributor.authorHaruma, K.en_US
dc.date.accessioned2015-01-07T15:23:50Z
dc.date.available2016-03-02T19:36:56Zen
dc.date.issued2015-01en_US
dc.identifier.citationShiotani, A.; Kusunoki, H.; Ishii, M.; Imamura, H.; Manabe, N.; Kamada, T.; Hata, J.; Merchant, J. L.; Haruma, K. (2015). "Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea‐predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH." Neurogastroenterology & Motility (1): 82-91.en_US
dc.identifier.issn1350-1925en_US
dc.identifier.issn1365-2982en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/109926
dc.description.abstractBackground Serotonin type 3 receptor (5‐ HT 3 R) antagonists are potentially useful therapeutic agents for diarrhea‐predominant irritable bowel syndrome ( IBS ‐D). To identify biomarkers predicting effectiveness of the 5‐ HT 3 R antagonist (ramosetron) in IBS ‐D. Methods Irritable bowel syndrome‐D Japanese subjects received 2.5 or 5  μ g 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 TPH 1 and TPH 2 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 TPH 1 ( p  = 0.02) expression were significantly higher in the ramosetron responders than in the non‐responders. The frequencies of the TPH 1 rs4537731G allele in linkage disequilibrium with the TPH 1 rs7130929 T allele (11.5% vs 50%, p  = 0.003; OR : 12; 95% CI: 2.1–69) along with TPH 1 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 TPH 1 rs211105 T/T than those with the G allele. Conclusions & Inferences TPH 1 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. Colonic mucosal S100A and TPH mRNA expression levels and TPH1 SNPs were analyzed in 42 treated patients. Increased S100A10 and TPH1 expression and TPH1 high producer SNPs appear to be associated with not only diarrhea symptoms, but also greater ramosetron effectiveness in IBS‐D patients.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.subject.otherTPH 1 Rs211105en_US
dc.subject.otherSerotonin Type 3 Receptor Antagonistsen_US
dc.subject.otherResistanceen_US
dc.titlePilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea‐predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPHen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelInternal Medicine and Specialtiesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/109926/1/nmo12473.pdf
dc.identifier.doi10.1111/nmo.12473en_US
dc.identifier.sourceNeurogastroenterology & Motilityen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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