TY - JOUR
T1 - Pharmacogenetics of low dose clonidine in irritable bowel syndrome
AU - Camilleri, M.
AU - Busciglio, I.
AU - Carlson, P.
AU - McKinzie, S.
AU - Burton, D.
AU - Baxter, K.
AU - Ryks, M.
AU - Zinsmeister, A. R.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Adrenergic
KW - G protein
KW - GNβ3
KW - Receptor
KW - SLC6A4
KW - Serotonergic
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U2 - 10.1111/j.1365-2982.2009.01263.x
DO - 10.1111/j.1365-2982.2009.01263.x
M3 - Article
C2 - 19309415
AN - SCOPUS:62449290346
SN - 1350-1925
VL - 21
SP - 399
EP - 410
JO - Neurogastroenterology and Motility
JF - Neurogastroenterology and Motility
IS - 4
ER -