Department of Psychology, University of Nebraska-Lincoln, Lincoln, 221 Burnett Hall, PO Box 880308, NE 68588-0308, USA.
Drug Alcohol Depend. 2011 Dec 15;119(3):e31-8. doi: 10.1016/j.drugalcdep.2011.05.025. Epub 2011 Jun 14.
Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses.
Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (n=439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression.
In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p=0.005) and between rs1004212 and alcohol problems (p=0.009). In women, there were weak associations between rs10146997 and TIME estimation (p=0.03); and between rs1004212 and drug problems (p=0.03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro.
Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction.
成瘾的部分遗传易感性可能由冲动性介导。本研究调查了冲动性、物质使用问题和六个神经连接蛋白 3（NRXN3）多态性之间的关系。神经连接蛋白（NRXNs）是突触前跨膜蛋白，在突触的发育和功能中起作用。
采用巴瑞特冲动量表第 11 版（BIS-11）、无聊倾向量表（BPS）和 TIME 范式评估冲动性；采用密歇根酒精筛查测试（MAST）评估酒精问题；采用药物滥用筛查测试（DAST-20）评估药物问题；采用一个问题评估常规烟草使用情况。参与者（n=439 名白种人，64.7%为女性）捐赠了口腔细胞进行基因分型。对 6 个 NRXN3 多态性进行了基因分型：rs983795、rs11624704、rs917906、rs1004212、rs10146997 和 rs8019381。进行双荧光素酶测定以确定 rs917906 的等位基因变异是否调节基因表达。
一般来说，经常使用烟草和/或有酒精或药物问题的人冲动性显著更高。在男性中，rs11624704 与注意力冲动性（p=0.005）之间存在适度关联，rs1004212 与酒精问题（p=0.009）之间存在适度关联。在女性中，rs10146997 与 TIME 估计（p=0.03）之间存在弱关联；rs1004212 与药物问题（p=0.03）之间存在弱关联。双荧光素酶测定表明，rs917906 的 C 和 T 等位基因在体外不能差异调节基因表达。
冲动性、物质使用问题和 NRXN3 多态性之间的关联可能具有性别特异性。冲动性与物质使用问题有关，可能为成瘾提供一个有用的中间表型。
