Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome
Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome
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DOI：
10.1371/journal.pone.0048135
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发表时间：
2012-10-23
期刊：
影响因子：
3.7
通讯作者：
Kaptchuk, Ted J.
中科院分区：
文献类型：
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作者：
Hall, Kathryn T.;Lembo, Anthony J.;Kaptchuk, Ted J.
识别潜在的安慰剂应答者对临床实践和试验设计具有重要意义。儿茶酚-O-甲基转移酶（COMT）是多巴胺催化剂中的一种重要酶，在奖赏、疼痛、记忆和学习等安慰剂效应相关过程中起着关键作用。我们假设COMT功能val 158 met多态性是安慰剂效应的预测因子，并在先前报道的肠易激综合征（IBS）随机对照试验中的104例患者中验证了我们的假设。本研究的三个治疗组为：无治疗（“等待名单”）、单独安慰剂治疗（“有限”）和安慰剂治疗“增强”，并伴有支持性患者-医疗保健提供者互动。主要结果指标是治疗3周后IBS症状严重程度量表（IBS-SSS）较基线的变化。在回归模型中，COMT val 158 met中的蛋氨酸等位基因数量与安慰剂应答呈线性相关，如通过IBS-SSS变化测量的（p = 0.035）。最强的安慰剂反应发生在接受强化安慰剂治疗的met/met纯合子中，在有限的安慰剂治疗中观察到较小的met/met相关效应，在等待名单对照中没有影响。这些数据支持我们的假设，即COMT val 158 met多态性是安慰剂反应的潜在生物标志物。
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.