The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients
The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients
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DOI：
10.1016/j.pain.2005.03.032
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发表时间：
2005-07-01
期刊：
影响因子：
7.4
通讯作者：
Skorpen, F
中科院分区：
文献类型：
--
作者：
Rakvåg, TT;Klepstad, P;Skorpen, F
儿茶酚-O-甲基转移酶（COMT）使神经系统中的多巴胺、肾上腺素和去甲肾上腺素失活。常见的功能多态性（Val 158 Met）导致COMT酶活性的三至四倍变化，Met形式显示较低的酶活性。Val 158 Met多态性影响疼痛感知，Met/Met基因型受试者对实验性疼痛的反应最明显。基于这些信息，我们分析了COMT Val 158 Met多态性对癌症疼痛患者中吗啡疗效的影响。我们对207例接受吗啡治疗的高加索癌症患者的Val 158 Met多态性进行了基因分型，并比较了基因型组之间的吗啡剂量、吗啡和吗啡代谢物的血清浓度。与瓦尔/Met（117 +/- 100 mg/24 h; n = 96）和Met/Met基因型（95 +/- 99 mg/24 h; n = 67）组相比，具有瓦尔/瓦尔基因型（n = 44）的患者需要更多的吗啡（155 160 mg/24 h）（P = 0.025）。这种差异不能用其他因素来解释，如吗啡治疗的持续时间，性能状态，自诊断以来的时间，感知疼痛强度，不良症状或死亡时间。这些结果表明，COMT基因的遗传变异可能导致吗啡治疗癌症疼痛的疗效差异。(C)2005年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Catechol-O-methyltransferase (COMT) inactivates dopamine, epinephrine and norepinephrine in the nervous system. A common functional polymorphism (Val158Met) leads to a three-to-four-fold variation in the COMT enzyme activity, the Met form displaying lower enzymatic activity. The Val158Met polymorphism affects pain perception, and subjects with the Met/Met genotype have the most pronounced response to experimental pain. Based on this information we analyzed the influence from the COMT Val158Met polymorphism on the efficacy of morphine in a cohort of patients suffering from cancer pain. We genotyped 207 Caucasian cancer patients on morphine treatment with respect to the Val158Met polymorphism and compared the morphine doses, serum concentrations of morphine and morphine metabolites between the genotype groups. Patients with the Val/Val genotype (n = 44) needed more morphine (155 160 mg/24 h) when compared to the Val/Met (117 +/- 100 mg/24 h; n = 96) and the Met/Met genotype (95 +/- 99 mg/24 h; n = 67) groups (P = 0.025). This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, perceived pain intensity, adverse symptoms, or time until death. These results suggest that genetic variation in the COMT gene may contribute to variability in the efficacy of morphine in cancer pain treatment. (C) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.