Pharmacogenetics of low dose clonidine in irritable bowel syndrome

• Published in: Neurogastroenterology and motility 2009-04, Vol.21 (4), p.399-410
• Main Authors: Camilleri, M., Busciglio, I., Carlson, P., Mckinzie, S., Burton, D., Baxter, K., Ryks, M., Zinsmeister, A. R.
• Format: Article
• Language: English
• Subjects: adrenergic; Adrenergic alpha-Agonists - administration & dosage; Clonidine - administration & dosage; Dose-Response Relationship, Drug; Female; G protein; GNβ3; Heterotrimeric GTP-Binding Proteins - genetics; Humans; Irritable Bowel Syndrome - drug therapy; Irritable Bowel Syndrome - genetics; Male; Pharmacogenetics; Polymorphism, Single Nucleotide; receptor; Receptors, Adrenergic, alpha-2 - genetics; serotonergic; Serotonin Plasma Membrane Transport Proteins - genetics; SLC6A4
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/j.1365-2982.2009.01263.x

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