Pharmacogenetics of Low Dose Clonidine in Irritable Bowel Syndrome

Overview

Journal Neurogastroenterol Motil

Specialties Gastroenterology
Neurology

Date 2009 Mar 25

PMID 19309415

Citations 11

Authors

M Camilleri

I Busciglio

P Carlson

S McKinzie

D Burton

K Baxter

M Ryks

A R Zinsmeister

Affiliations

Soon will be listed here.

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: 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.

Citing Articles

Current and Future Therapeutic Options for Irritable Bowel Syndrome with Diarrhea and Functional Diarrhea.

Ramos G, Camilleri M Dig Dis Sci. 2022; 68(5):1677-1690.

PMID: 36376576 DOI: 10.1007/s10620-022-07700-8.

G protein beta 3() C825T polymorphism and irritable bowel syndrome susceptibility: an updated meta-analysis based on eleven case-control studies.

Jiang D, Huang D, Cai W, Li T, Wang Y, Chen H Oncotarget. 2018; 9(2):2770-2781.

PMID: 29416810 PMC: 5788678. DOI: 10.18632/oncotarget.23449.

Pharmacological Approach for Managing Pain in Irritable Bowel Syndrome: A Review Article.

Chen L, Ilham S, Feng B Anesth Pain Med. 2017; 7(2):e42747.

PMID: 28824858 PMC: 5556397. DOI: 10.5812/aapm.42747.

Pharmacogenetics and the treatment of functional gastrointestinal disorders.

Halawi H, Camilleri M Pharmacogenomics. 2017; 18(11):1085-1094.

PMID: 28686075 PMC: 5591464. DOI: 10.2217/pgs-2017-0049.

Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.

Hall K, Kossowsky J, Oberlander T, Kaptchuk T, Saul J, Wyller V Pharmacogenomics J. 2016; 16(5):454-60.

PMID: 27457818 PMC: 5028250. DOI: 10.1038/tpj.2016.53.

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