Pharmacogenetics of low dose clonidine in irritable bowel syndrome

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 2009

Fingerprint

Irritable Bowel Syndrome
Pharmacogenetics
Clonidine
Satiation
Compliance
Stomach
Adrenergic Agents
Neurotransmitter Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Pain Threshold
Genes
Serotonin
Gases
Genotype
Pain
Health

Keywords

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

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Gastroenterology
  • Physiology

Cite this

Camilleri, M., Busciglio, I., Carlson, P., McKinzie, S., Burton, D., Baxter, K., ... 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

Pharmacogenetics of low dose clonidine in irritable bowel syndrome. / Camilleri, Michael; Busciglio, I.; Carlson, P.; McKinzie, S.; Burton, D.; Baxter, K.; Ryks, M.; Zinsmeister, A. R.

In: Neurogastroenterology and Motility, Vol. 21, No. 4, 04.2009, p. 399-410.

Research output: Contribution to journalArticle

Camilleri, M, Busciglio, I, Carlson, P, McKinzie, S, Burton, D, Baxter, K, Ryks, M & Zinsmeister, AR 2009, 'Pharmacogenetics of low dose clonidine in irritable bowel syndrome', Neurogastroenterology and Motility, vol. 21, no. 4, pp. 399-410. https://doi.org/10.1111/j.1365-2982.2009.01263.x
Camilleri, Michael ; Busciglio, I. ; Carlson, P. ; McKinzie, S. ; Burton, D. ; Baxter, K. ; Ryks, M. ; Zinsmeister, A. R. / Pharmacogenetics of low dose clonidine in irritable bowel syndrome. In: Neurogastroenterology and Motility. 2009 ; Vol. 21, No. 4. pp. 399-410.
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