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

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

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Title: Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome
Author: Hall, Kathryn 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 J.

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Citation: Hall, K. T., J. Kossowsky, T. F. Oberlander, T. J. Kaptchuk, J. P. Saul, V. B. Wyller, E. Fagermoen, et al. 2016. “Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.” The pharmacogenomics journal 16 (5): 454-460. doi:10.1038/tpj.2016.53. http://dx.doi.org/10.1038/tpj.2016.53.
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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 double-blinded 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.
Published Version: doi:10.1038/tpj.2016.53
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028250/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:30371170
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