Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence:: Results from the VA cooperative study
Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence:: Results from the VA cooperative study
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DOI：
10.1111/j.1530-0277.2007.00339.x
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Krystal, John H.
中科院分区：
文献类型：
--
作者：
Gelernter, Joel;Gueorguieva, Ralitza;Krystal, John H.
背景：酒精依赖（AD）的药物治疗尚处于发展的早期阶段；目前可用的药物疗效有限。在开始治疗之前，根据遗传标记识别出最有可能对特定药物疗法产生反应的患者，将具有临床价值。之前的一份报告表明，在阿片类药物阻断药物纳曲酮 (NTX) 的短期（3 个月）治疗中，编码 mu 阿片受体 (Asn40Asp) 的基因位点的功能变异就是这样一个标记。方法：我们研究了 3 个阿片受体基因 OPRM1、OPRD1 和 OPRK1（编码 mu、delta 和 kappa 阿片受体）中每一个的多态性变异。分别包括 OPRM1 Asn40Asp 变体，作为参加退伍军人事务合作研究 425“纳曲酮治疗酒精依赖”的 215 名酒精依赖男性受试者对 NTX 或安慰剂反应的预测因子。 结果：在 3 个月的时间点，治疗条件、年龄和每个饮酒日的治疗前饮酒次数都是复发率和复发时间的显着预测因子（p < 0.05）。复发。尽管 NTX 对 CSP 425 整个样本中的重度饮酒复发没有显着影响，但它显着减少了提供 DNA 进行分析的亚组（即本研究样本）的复发。研究的任何个体单核苷酸多态性与 NTX 治疗反应之间没有显着的相互作用。结论：这些结果不支持 OPRM1 Asn40Asp 多态性与 AD 的 NTX 治疗反应之间的关联。
Background: Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the mu opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX).Methods: We studied polymorphic variants at each of the 3 opioid receptor genes-OPRM1, OPRD1, and OPRK1, which encode the mu, delta, and kappa opioid receptors, respectively-including the OPRM1 Asn40Asp variant-as predictors of response to NTX or placebo in 215 alcohol-dependent male subjects who participated in Veterans Affairs Cooperative Study 425, "Naltrexone in the Treatment of Alcohol Dependence."Results: At the 3-month time point, treatment condition, age, and the pretreatment number of drinks per drinking day were all significant (p < 0.05) predictors of the rate of relapse and time to relapse. Although NTX had no significant effect on relapse to heavy drinking in the overall sample in CSP 425, it significantly reduced relapse in the subgroup that provided DNA for analysis (i.e., the present study sample). There were no significant interactions between any individual single nucleotide polymorphisms studied and NTX treatment response.Conclusions: These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.