Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome
Hall, Karhryn T.; Kossowsky, Joe; Oberlander, Tim F.; Kaptchuk, Ted J.; Saul, J. Philip; Wyller, Vegard Bruun; Fagermoen, Even; Sulheim, Dag; Gjerstad, Johannes; Winger, Anette; Mukamal, Kenneth Jay
Peer reviewed, Journal article
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http://hdl.handle.net/11250/2492599Utgivelsesdato
2016Metadata
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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 doubleblinded
clonidine versus placebo trial, was conducted (N=104). Patients homozygous for rs4680
high-activity allele randomized to clonidine took 2,500 fewer steps compared to placebo
(pinteraction=0.04). There were no differences between clonidine and placebo amongst patients
with COMT low-activity alleles. Similar gene-drug interactions were observed for sleep
(pint=0.003) and quality of life (pint=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.