Pharmacogenetics of low dose clonidine in irritable bowel syndrome

M. Camilleri, I. Busciglio, P. Carlson, S. McKinzie, D. Burton, K. Baxter, M. Ryks, A. R. Zinsmeister

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Adrenergic and serotonergic (ADR-SER) mechanisms alter gut (gastrointestinal, GI) sensorimotor functions. We aimed to determine whether candidate ADR-SER genes affect GI responses to low dose clonidine (CLO) in humans. Forty healthy and 120 irritable bowel syndrome (IBS) participants received CLO, 0.1 mg or 0.15 mg b.i.d., for 6 days. At baseline and post-CLO, we measured: gastric volume (GV); satiation volume; rectal compliance, sensation thresholds and ratings with distensions. Genetic variations tested were: α2A (C-1291G), α2C (Del 322-325), GNβ3 (C825T) and solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) (serotonin transporter linked polymorphic region). CLO reduced volume to satiation (P = 0.002), postprandial GV (P < 0.001), sensation threshold for pain (<0.001); CLO increased rectal compliance (P = 0.024). There were significant associations between post-CLO responses and gene variations for †GV (α2A and SLC6A4), rectal sensation of gas (α2A, GNβ3), urgency (α2A); and pain (GNβ3 and SLC6A4); and rectal compliance (SLC6A4). α2A, GNβ3 and SLC6A4 genotypes significantly modify responses to CLO on sensory and motor GI functions in health and IBS.

Original languageEnglish (US)
Pages (from-to)399-410
Number of pages12
JournalNeurogastroenterology and Motility
Volume21
Issue number4
DOIs
StatePublished - Apr 1 2009

Keywords

  • Adrenergic
  • G protein
  • GNβ3
  • Receptor
  • SLC6A4
  • Serotonergic

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Fingerprint Dive into the research topics of 'Pharmacogenetics of low dose clonidine in irritable bowel syndrome'. Together they form a unique fingerprint.

  • Cite this

    Camilleri, M., Busciglio, I., Carlson, P., McKinzie, S., Burton, D., Baxter, K., Ryks, M., & Zinsmeister, A. R. (2009). Pharmacogenetics of low dose clonidine in irritable bowel syndrome. Neurogastroenterology and Motility, 21(4), 399-410. https://doi.org/10.1111/j.1365-2982.2009.01263.x