Department of Psychobiology, Faculty of Psychology, Complutense University of Madrid, Campus de Somosaguas, 28223, Madrid, Spain.
Mol Genet Genomics. 2014 Jun;289(3):279-89. doi: 10.1007/s00438-013-0809-x. Epub 2014 Jan 10.
Drug addiction is a complex disease with overlapping stages and influenced by multiple environmental and genetic factors. In addition to neurobiological changes, repeated drug exposure modulates affective responses to drug stimuli including visual cues. Here, we made a preliminary screening among ten Single Nucleotide Polymorphisms (SNP) of the CNR1 (rs806368, rs1049353, rs6454674, rs7766029), FAAH (rs324420, rs12075550), DRD2 (rs6277), ANKK1 (rs1800497), COMT (rs4680), and OPRM1 (rs1799971) genes to identify that SNPs that were more directly associated with alcohol, tobacco and/or cannabis consumption in young individuals (n = 91). Also, affective rating for alcohol-, tobacco- and cannabis-related pictures was examined in each individual. Our results make it possible to select the rs324420 SNP (C385A) of the FAAH gene for further analysis. Increasing the sample size up to n = 185 we found that the homozygous CC C385A SNP genotype was associated with risky alcohol use (p = 0.006, odds ratio 2.38). Subsequently, we replicated this genetic association with risky alcohol use using another independent sample. Risky drinkers (mean 166.8 g pure alcohol) and smokers (more than 15 cigarettes) rated drug pictures more positively (p < 0.001) and they showed a strong positive correlation with drug use during weekends, which is the period in which the first problematic experiences with alcohol and other drugs appear (initial stages of the drug addiction process). As conclusion, because drug addiction is a multi-step process and a preventable disease, our results indicate that the FAAH C385A SNP is one of the most promising candidates for individuals who are at higher risk for alcohol problems.
药物成瘾是一种复杂的疾病,具有重叠的阶段,并受到多种环境和遗传因素的影响。除了神经生物学变化外,反复的药物暴露还会调节对药物刺激(包括视觉线索)的情感反应。在这里,我们在十个单核苷酸多态性(SNP)中进行了初步筛选,这些 SNP 分别位于 CNR1(rs806368、rs1049353、rs6454674、rs7766029)、FAAH(rs324420、rs12075550)、DRD2(rs6277)、ANKK1(rs1800497)、COMT(rs4680)和 OPRM1(rs1799971)基因中,以确定与年轻人的酒精、烟草和/或大麻消费更直接相关的 SNP(n = 91)。此外,还在每个个体中检查了对与酒精、烟草和大麻相关的图片的情感评分。我们的研究结果使 FAAH 基因的 rs324420 SNP(C385A)能够进行进一步的分析。我们将样本量增加到 n = 185,发现 FAAH 基因的纯合 CC C385A SNP 基因型与危险的饮酒行为有关(p = 0.006,优势比 2.38)。随后,我们使用另一个独立的样本复制了这种与危险饮酒相关的遗传关联。危险饮酒者(平均 166.8 克纯酒精)和吸烟者(超过 15 支香烟)对药物图片的评价更积极(p < 0.001),并且他们与周末的药物使用之间存在强烈的正相关关系,而周末是首次出现与酒精和其他药物相关的问题体验的时期(药物成瘾过程的初始阶段)。因此,由于药物成瘾是一个多步骤的过程和一种可预防的疾病,我们的结果表明,FAAH C385A SNP 是那些有更高酒精问题风险的个体的最有希望的候选者之一。