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

Pharmacogenomics J. 2016 Oct;16(5):454-60. doi: 10.1038/tpj.2016.53. Epub 2016 Jul 26.

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adrenergic alpha-2 Receptor Agonists / adverse effects
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Catechol O-Methyltransferase / genetics*
  • Child
  • Clonidine / adverse effects
  • Clonidine / therapeutic use*
  • Double-Blind Method
  • Exercise Tolerance / drug effects
  • Fatigue Syndrome, Chronic / diagnosis
  • Fatigue Syndrome, Chronic / drug therapy*
  • Fatigue Syndrome, Chronic / enzymology
  • Fatigue Syndrome, Chronic / genetics
  • Female
  • Genetic Association Studies
  • Homozygote
  • Humans
  • Male
  • Norway
  • Orthostatic Intolerance / chemically induced
  • Orthostatic Intolerance / enzymology
  • Orthostatic Intolerance / genetics
  • Pharmacogenetics
  • Pharmacogenomic Variants*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Quality of Life
  • Risk Assessment
  • Risk Factors
  • Sleep / drug effects
  • Treatment Outcome

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • COMT protein, human
  • Catechol O-Methyltransferase
  • Clonidine