Genetic variation in catechol-O-methyltransferase modifies effects of clonidine treatment in chronic fatigue syndrome.
Pharmacogenomics J
; 16(5): 454-60, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27457818
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Catecol O-Metiltransferasa
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Síndrome de Fatiga Crónica
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Clonidina
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Polimorfismo de Nucleótido Simple
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Agonistas de Receptores Adrenérgicos alfa 2
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Variantes Farmacogenómicas
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Child
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Female
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Humans
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Male
País como asunto:
Europa
Idioma:
En
Año:
2016
Tipo del documento:
Article