title: Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.
abstract: Clonidine, an α2-adrenergic receptor agonist, decreases circulating norepinephrine and epinephrine, attenuating sympathetic activity. Although catechol-O-methyltransferase (COMT) metabolizes catecholamines, main effectors of sympathetic function, COMT genetic variation effects on clonidine treatment are unknown. Chronic fatigue syndrome (CFS) is hypothesized to result in part from dysregulated sympathetic function. A candidate gene analysis of COMT rs4680 effects on clinical outcomes in the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial (NorCAPITAL), a randomized double-blinded clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680 high-activity allele randomized to clonidine took 2500 fewer steps compared with placebo (Pinteraction=0.04). There were no differences between clonidine and placebo among patients with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep (Pinteraction=0.003) and quality of life (Pinteraction=0.018). Detrimental effects of clonidine in the subset of CFS patients homozygous for COMT high-activity allele warrant investigation of potential clonidine-COMT interaction effects in other conditions.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.|Harvard Medical School, Boston, MA, USA.
authors.forename: K T
authors.initials: KT
authors.lastname: Hall
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Department of Anesthesiology Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.|Department of Clinical Psychology and Psychotherapy, University of Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Kossowsky
authors.affiliation: Child and Family Research Institute, Department of Pediatrics, and School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: T F
authors.initials: TF
authors.lastname: Oberlander
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.|Program in Placebo Studies, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Kaptchuk
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Saul
authors.affiliation: Department of Paediatrics, Akershus University Hospital, Lørenskog, Norway.
authors.forename: V B
authors.initials: VB
authors.lastname: Wyller
authors.affiliation: Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Fagermoen
authors.affiliation: Department of Pediatrics, Lillehammer County Hospital, Brumunddal, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Sulheim
authors.affiliation: National Institute of Occupational Health, Department, Oslo, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Gjerstad
authors.affiliation: Department of Nursing and Health Promotion, Faculty of Health, Oslo University College of Applied Sciences, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Winger
authors.affiliation: Harvard Medical School, Boston, MA, USA.|Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000293:Adolescent; D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D003000:Clonidine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects; D015673:Fatigue Syndrome, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008297:Male; D009664:Norway; D054971:Orthostatic Intolerance / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011788:Quality of Life; D018570:Risk Assessment; D012307:Risk Factors; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D003000:Clonidine