Wojnar Marcin, Brower Kirk J, Strobbe Stephen, Ilgen Mark, Matsumoto Halina, Nowosad Izabela, Sliwerska Elzbieta, Burmeister Margit
Department of Psychiatry, University of Michigan, Ann Arbor, Michigan 48109, USA.
Alcohol Clin Exp Res. 2009 Apr;33(4):693-702. doi: 10.1111/j.1530-0277.2008.00886.x. Epub 2009 Jan 27.
The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients.
The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures.
Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger.
The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies.
本研究旨在探讨酒精依赖患者样本中，中枢5-羟色胺（5-HT）和多巴胺功能的遗传标记与治疗后复发风险之间的关系。
该研究纳入了来自波兰成瘾治疗项目的154名患者，这些患者符合酒精依赖的DSM-IV标准。在评估了人口统计学特征、酒精使用严重程度、自杀倾向、冲动性、抑郁、绝望以及基线时的酒精使用严重程度后，对患者进行了约1年的随访以评估治疗结果。测试了几个基因（TPH2、SLC6A4、HTR1A、HTR2A、COMT和BDNF）中的基因多态性作为复发的预测指标（定义为随访期间的任何饮酒行为），同时控制基线测量值。
在154名符合条件的患者中，123名（80%）完成了随访，其中48%（n = 59）的个体复发。携带BDNF基因Val66Met多态性的Val等位基因和COMT基因Val158Met多态性的Met等位基因的患者更易复发。在调整基线测量值和其他显著的遗传标记后，只有BDNF Val/Val基因型可预测治疗后复发[比值比（OR）= 2.62；p = 0.019]以及复发时间（OR = 2.57；p = 0.002）。当分析仅限于有酒精依赖家族史的患者（n = 73）时，BDNF Val/Val基因型与复发（OR = 5.76，p = 0.0045）以及复发时间（风险比 = 4.93，p = 0.001）之间的关联更强。
BDNF基因Val66Met多态性与酒精依赖治疗患者的较高复发风险和更早复发相关。该研究提示了酒精依赖中遗传标记与治疗结果之间的关系。由于本研究进行了大量的统计检验，且关于遗传学和复发的文献非常新颖，因此这些结果应被视为产生假设，需要在独立研究中进行重复验证。
