Associations among types of impulsivity, substance use problems and Neurexin-3 polymorphisms

Background: 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. Methods: 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. Results: 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. Conclusions: 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.