Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1.
Neurogastroenterol Motil
; 27(1): 82-91, 2015 Jan.
Article
en En
| MEDLINE
| ID: mdl-25428414
ABSTRACT
BACKGROUND:
Serotonin type 3 receptor (5-HT3 R) antagonists are potentially useful therapeutic agents for diarrhea-predominant irritable bowel syndrome (IBS-D). To identify biomarkers predicting effectiveness of the 5-HT3 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. KEYRESULTS:
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Triptófano Hidroxilasa
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Bencimidazoles
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Proteínas S100
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Anexina A2
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Síndrome del Colon Irritable
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Diarrea
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Biomarcadores Farmacológicos
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Antagonistas del Receptor de Serotonina 5-HT3
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2015
Tipo del documento:
Article