Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain:: OPRM1 and COMT gene
Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain:: OPRM1 and COMT gene
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DOI：
10.1016/j.pain.2006.10.023
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发表时间：
2007-07-01
期刊：
影响因子：
7.4
通讯作者：
Klepstad, Pål
中科院分区：
文献类型：
--
作者：
Reyes-Gibby, Cielito C.;Shete, Sanjay;Klepstad, Pål
疼痛是一种复杂的人类特征。很可能是多个基因的相互作用，每个基因都有一个小的个体效应，沿着环境因素的影响，而不是单个基因单独影响阿片类药物的临床疗效。编码μ-阿片受体（A118 G）和儿茶酚-O-甲基转移酶（Vall 58 Met）的基因多态性可能是阿片类药物疗效的重要调节剂。我们评估了OPRM 1和COMT基因在预测用于癌症疼痛缓解的吗啡剂量中的联合作用。我们使用的基因型和临床数据从207例住院患者接受稳定剂量吗啡治疗至少3天的姑息医学专家的吗啡药代动力学研究。结果显示，基因型组对吗啡剂量的需求存在显著差异：COMT Va 1/Va 1和Va 1/Met基因型携带者分别需要63%和23%的吗啡剂量，与Met/Met基因型携带者相比，需要更高的吗啡剂量（= 0.02）。与AA基因型携带者相比，OPRM 1 GG基因型携带者需要高93%的吗啡剂量（p = 0.012）。当我们探索联合效应时，我们发现OPRM 1 AA和COMT Met/Met基因型携带者需要最低的吗啡剂量来实现疼痛缓解（87 mg/24 h; 95%CI = 507，116），而那些既没有Met/Met也没有AA基因型的人需要最高的吗啡剂量（147 mg/24 h; 95%CI = 100，180）。即使在多变量分析中控制了人口统计学和临床变量后，Met/Met和AA基因型的显著联合效应（p < 0.012）仍然存在。未来的研究需要进一步表征多个基因的联合作用，沿着人口统计学和临床变量，在预测阿片类药物剂量。(C)2006年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and catechol-O-methyl transferase (Vall 58Met) may be important modulators of opioid efficacy. We assessed joint effects of the OPRM1 and COMT genes in predicting morphine dose for cancer pain relief. We used genotype and clinical data from a pharmacokinetic study of morphine in 207 inpatients treated with stable morphine dose for at least 3 days by Palliative Medicine Specialists. Results showed significant variation in morphine dose requirement by genotype groups: carriers of COMT Va1/Va1 and Va1/Met genotype required 63% and 23%, respectively, higher morphine dose compared to carriers of Met/Met genotype) = 0.02). Carriers of OPRM1 GG genotype required 93% higher morphine dose compared to carriers of AA genotypes (p = 0.012). When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI = 507,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI = 100,180). The significant joint effects for the Met/Met and AA genotypes (p < 0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose. (C) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.