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

被引：21

作者：

Hall, K. T. ^{[1
,2
]}

Kossowsky, J. ^{[2
,3
,4
]}

Oberlander, T. F. ^{[5
,6
]}

Kaptchuk, T. J. ^{[2
,7
,8
]}

Saul, J. P. ^{[9
]}

Wyller, V. B. ^{[10
]}

Fagermoen, E. ^{[11
]}

Sulheim, D. ^{[12
]}

Gjerstad, J. ^{[13
]}

Winger, A. ^{[14
]}

Mukamal, K. J. ^{[2
,7
]}

机构：

[1] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave, Boston, MA 02215 USA

[2] Harvard Med Sch, Boston, MA USA

[3] Harvard Med Sch, Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA

[4] Univ Basel, Dept Clin Psychol & Psychotherapy, Basel, Switzerland

[5] Univ British Columbia, Dept Pediat, Child & Family Res Inst, Vancouver, BC, Canada

[6] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada

[7] Harvard Med Sch, Div Gen Med & Primary Care, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA

[8] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA USA

[9] Med Univ South Carolina, Div Cardiol, Dept Pediat, Charleston, SC USA

[10] Akershus Univ Hosp, Dept Paediat, Lorenskog, Norway

[11] Oslo Univ Hosp, Dept Anesthesiol & Crit Care, Oslo, Norway

[12] Lillehammer Cty Hosp, Dept Pediat, Brumunddal, Norway

[13] Natl Inst Occupat Hlth, Oslo, Norway

[14] Univ Oslo, Coll Appl Sci, Fac Hlth, Dept Nursing & Hlth Promot, Oslo, Norway

来源：

PHARMACOGENOMICS JOURNAL | 2016年 / 16卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

LOW-DOSE CLONIDINE; BLOOD-PRESSURE; VAL158MET POLYMORPHISM; COMT; ADOLESCENTS; CANCER; TRIAL; PHARMACOGENETICS; HYPERTENSION; MODULATION;

D O I：

10.1038/tpj.2016.53

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Clonidine, an alpha 2-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 (P-interaction = 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 (P-interaction = 0.003) and quality of life (P-interaction =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.

引用

页码：454 / 460

页数：7

共 44 条

[31] Tolcapone Effects on Gating, Working Memory, and Mood Interact with the Synonymous Catechol-O-methyltransferase rs4818C/G Polymorphism [J].