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Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.


ABSTRACT: Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS). The three treatment arms from this study were: no-treatment ("waitlist"), placebo treatment alone ("limited") and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS) after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p?=?.035). The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

SUBMITTER: Hall KT 

PROVIDER: S-EPMC3479140 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

Hall Kathryn T KT   Lembo Anthony J AJ   Kirsch Irving I   Ziogas Dimitrios C DC   Douaiher Jeffrey J   Jensen Karin B KB   Conboy Lisa A LA   Kelley John M JM   Kokkotou Efi E   Kaptchuk Ted J TJ  

PloS one 20121023 10


Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT), an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized  ...[more]

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