多巴胺和阿片受体基因多态性与美沙酮维持治疗反应的关联。
Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment.
作者信息
Crettol Séverine, Besson Jacques, Croquette-Krokar Marina, Hämmig Robert, Gothuey Isabelle, Monnat Martine, Déglon Jean-Jacques, Preisig Martin, Eap Chin B
机构信息
Unité de Biochimie et de Psychopharmacologie Clinique, Centre de Neurosciences Psychiatriques, Département de Psychiatrie, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Hôpital de Cery, CH-1008 Prilly-Lausanne, Switzerland.
出版信息
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Oct 1;32(7):1722-7. doi: 10.1016/j.pnpbp.2008.07.009. Epub 2008 Jul 17.
BACKGROUND
Genetic variations of the dopamine and opioid receptors could influence the response to methadone maintenance treatment (MMT).
METHODS
We included 238 MMT patients according to their response to treatment and methadone dosing, along with 217 subjects without substance dependence. All were genotyped for polymorphisms of the dopamine D1, D2, micro-opioid and delta-opioid receptor genes.
RESULTS
The polymorphisms of the micro-opioid (118A>G), delta-opioid (921T>C), dopamine D1 (DdeI) and D2 (TaqI A) receptor genes were not associated with response to MMT and methadone dosing, whereas an association was found with the dopamine D2 receptor (DRD2) 957C>T polymorphism. The 957CC carriers were more frequently non-responders to treatment (OR=2.4; p=0.02) and presented a fourfold shorter period of negative urine screening (p=0.02). No significant differences in allele frequencies were observed between the MMT patients and the control group, suggesting no association of the analyzed polymorphisms with opioid dependence.
CONCLUSIONS
These results suggest that DRD2 genotype may contribute to the understanding of the interindividual variability to the response to MMT.
背景
多巴胺和阿片受体的基因变异可能会影响美沙酮维持治疗（MMT）的效果。
方法
我们根据治疗反应和美沙酮剂量纳入了238例MMT患者，以及217例无物质依赖的受试者。对所有受试者的多巴胺D1、D2、微阿片和δ阿片受体基因多态性进行基因分型。
结果
微阿片受体（118A>G）、δ阿片受体（921T>C）、多巴胺D1（DdeI）和D2（TaqI A）受体基因的多态性与MMT反应及美沙酮剂量无关，而多巴胺D2受体（DRD2）957C>T多态性存在关联。957CC携带者对治疗无反应的频率更高（OR=2.4；p=0.02），且尿筛查阴性期缩短四倍（p=0.02）。MMT患者与对照组之间等位基因频率无显著差异，表明所分析的多态性与阿片类药物依赖无关。
结论
这些结果表明，DRD2基因型可能有助于理解个体对MMT反应的差异。
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