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Pharmacogenetics of low dose clonidine in irritable bowel syndrome.

Author(s): Camilleri M, Busciglio I, Carlson P, McKinzie S, Burton D, Baxter K, Ryks M, Zinsmeister AR

Affiliation(s): Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, MN 55905, USA. camilleri.michael@mayo.edu

Publication date & source: 2009-04, Neurogastroenterol Motil., 21(4):399-410.

Publication type: Randomized Controlled Trial; Research Support, N.I.H., Extramural

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: alpha2A (C-1291G), alpha2C (Del 322-325), GNbeta3 (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 DeltaGV (alpha2A and SLC6A4), rectal sensation of gas (alpha2A, GNbeta3), urgency (alpha2A); and pain (GNbeta3 and SLC6A4); and rectal compliance (SLC6A4). alpha2A, GNbeta3 and SLC6A4 genotypes significantly modify responses to CLO on sensory and motor GI functions in health and IBS.

Page last updated: 2009-10-20

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