Brain dopaminergic system: genetic variations, personality traits and alcohol addiction risk

Abstract

Background and Aim: Brain dopamine system is involved in response to reward and reward associated cue, predicted reward error estimation, learning and motivation. Genetic polymorphism of dopaminergic system in brains determines personality traits such as proneness to anxiety, hopelessness, impulsivity, openness to experience, which might increase vulnerability to various addictions. This study applies genotyping to determine genetic polymorphism for DRD2/ANKK1, COMT and SLC6A3 genes that are involved in dopaminergic activity. Carriers of COMT (rs4680) 472G>A variant have slower enzymatic rate of COMT leading to increased dopamine in frontal cortex which suppresses impulsive response to cue associated with reward; DRD2/ANKK1 (rs1800497) 2137G>A variant is associated with lower D2 receptor amount and lower affinity; SLC6A3 (rs27072) 328C>T variant results in increased activity of DAT1 transporter and decreased amount of extra-synaptic dopamine in ventral striatum. Attention to gene polymorphism and addiction related personality traits is the novelty of our research. Materials and Methods: Seventy four LSMU employees and patients from LSMU Neurosurgery Department were genotyped to determine MAF of chosen genetic variants. Risk of alcohol use disorder was assessed by Alcohol Use Disorders Identification Test (AUDIT). Personality traits will be assessed by specific scales: Barrat Impulsiveness Scale-11 (BIS-11) for impulsivity and impulsivity dimensions, Substance Use Risk Profile Scale (SURPS) for proneness to anxiety, hopelessness, impulsivity, and novelty seeking. Results: Frequency of alleles were as follows: COMT rs4680 A: MAF=0.48; DRD2/ANKK1 rs1800497 A MAF=0.22; SLC6A3 rs27072 T MAF=0.30. Milestones of the Project: To genotype and perform gene association and gene-gene interaction of DRD2/ ANKK1, COMT and SLC6A3 with personality traits and alcohol addiction in large population-based cohort.