aDepartment of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston bDepartment of Psychiatry and Behavioral Sciences, Baylor College of Medicine and Michael E. DeBakey V.A. Medical Center, MEDVAMC, Houston, Texas cDepartment of Psychiatry and Pharmacology and Toxicology, Virginia Commonwealth University Medical School, Richmond, Virginia, USA.
Pharmacogenet Genomics. 2014 Jul;24(7):370-3. doi: 10.1097/FPC.0000000000000055.
Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine β-hydroxylase (DβH). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the DβH gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low DβH activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal DβH activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.
最近的研究表明,多巴胺活性和功能水平的异质性可能有助于识别出对多巴胺增强型药物治疗反应更好的可卡因依赖患者亚组。在这里,我们假设在遗传上确定多巴胺代谢酶多巴胺β-羟化酶(DβH)水平较低的患者中,左旋多巴/卡比多巴治疗的反应会更大。71 名参加为期 12 周的随机双盲安慰剂对照左旋多巴/卡比多巴试验的可卡因依赖患者接受了 DβH 基因(DBH)多态性 rs1611115 的基因分型。我们的结果表明,对于接受左旋多巴治疗的低 DβH 活性基因型(CT/TT)的患者,与 CT/TT 基因型的安慰剂治疗患者相比,可卡因阳性尿液的几率在治疗过程中显著降低(P=0.004)。具有正常 DβH 活性基因型(CC)的个体对左旋多巴没有不同的反应。这些初步结果需要在一个更大的样本中,重点关注 DBH 多态性,以得到进一步证实。