3255 Association between dopaminergic genetic variants, COMTrs4680 and DRD2rs1076560, and alcohol consumption and reward behaviors in non-dependent drinkers

OBJECTIVES/SPECIFIC AIMS: The objective of this exploratory study is to evaluate the relationship between the individual genetic variants in COMTrs4680 and DRDrs1076560 and relevant alcohol use behaviors (i.e. alcohol consumption and reward processing behaviors) in non-dependent drinkers within experimentally controlled IV-ASA CAIS sessions. The overall goal of this study is to begin gathering data on the influence of individual genetic variants on alcohol consumption and other drinking-related behaviors. This will aid in the creation of a polygenic model of risk for AUD which will provide more insight into how the mesolimbic pathway is affected by alcohol use. METHODS/STUDY POPULATION: Study population: The sample included male and female non-dependent drinkers (N=149). Genotypes for functional polymorphisms in COMT (rs4680) and DRD2 (rs1076560) genes were determined for all subjects from blood samples obtained during screening. Alcohol consumption was assessed using the 90-day Timeline Followback Interviews (TLFB). Study population demographics: Self-reported gender (53.5% identified as male); Self-reported race (61.2% identified as white); Age ranged from 21-46 years old, with 22 years being the mode. Experiment: Free access (open-bar) intravenous alcohol self-administration (IV-ASA) using the computer-assisted alcohol infusion system (CAIS) paradigm; Subjects had the choice of pressing a button ad libitum for IV alcohol infusions during the session, neurobehavioral questionnaires were collected throughout the 2.5-hr alcohol infusion session. Primary outcome measures included: Total Rewards, Peak breath alcohol concentration (BrAC) achieved, and Total Ethanol consumed. Statistical Analyses: Conducted using SPSS IBM Statistics Versions 1.0.0-2482; non-dependent drinkers were organized into two groups based on their genotypes, minor allele carriers and major allele homozygotes. Outcome measures were compared between genotype groups using analysis of variance or non-parametric Mann-Whitney U-test as appropriate. RESULTS/ANTICIPATED RESULTS: -We expect the genetic makeup of the sample to be reflective of larger genome samples that are publically available (e.g. e!Ensembl) - Initial analysis for COMTrs4680 did not reveal significant effects on IV-ASA measures. Specifically, the majo DISCUSSION/SIGNIFICANCE OF IMPACT: Alcohol Use Disorder (AUD) affects millions of men and women globally. The heterogeneity within AUD individuals has made it difficult to identify biological and/or psychological factors that could be targeted for the development of treatments. By using the human laboratory model of free access IV-ASA, this study evaluated the relationship between dopaminergic genetic variants, COMTrs4680 and DRDrs1076560, and alcohol consumption in non-dependent drinkers within a controlled experimental environment. This study will begin to evaluate genetic and behavioral data that can be used to create a polygenic model of risk for AUD, which will provide more insight as to how the mesolimbic reward pathway is affected by alcohol use and contributes to risk for AUD.