Title
Influence of dopamine-related genes on problematic drinking, impulsivity and aggression in Korean male patients with alcohol use disorder

Authors
Heeyeon Kim1,3, Chun Il Park1,3, Hae Won Kim1,2, Jee In Kang1,3 & Se Joo Kim1,3
1Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Department of Medical Education, Yonsei University College of Medicine, Seoul, Republic of Korea
3Department of Psychiatry, Yonsei University College of Medicine, Seoul, Republic of Korea.




Objectives
The aim of the study was to examine the genetic influence of dopamine system on the problematic drinking, impulsivity and aggression in a Korean male population with alcohol use disorder (AUD).

Background
Recent evidence has suggested that abnormality of dopaminergic neurotransmission is implicated in the pathophysiology of AUD. Several studies have shown associations between dopamine-related gene variants and alcohol-related severity and cravings in patients with AUD.

Methods
We genotyped five single nucleotide polymorphisms (SNPs) (rs4532 in DRD1, rs2283265 in DRD2, rs6280 in DRD3, rs1800497 in ANKK1 and rs4680 in COMT) and a variable number of tandem repeats (VNTR) in DAT1 in 295 male patients with AUD. To analyze the genetic associations between dopamine system and severity of alcohol use or craving, we examined the Alcohol Use Disorders Identification Test and the Obsessive-Compulsive Drinking Scale (OCDS). Participants also completed the UPPS-P impulsive behavior scale and Buss-Perry Aggression Questionnaire (BPAQ). The analyses were conducted with the R package SNPassoc, statistical significance was set at p < 0.0083 after Bonferroni correction.

Results
A significant association was detected between DRD3 SNP rs6280 and OCDS score (p = 0.0061). With respect to impulsivity and aggression, rs4532 of DRD1 was significantly related to UPPS-P score (p = 0.0037). Although it did not reach statistical significance after correction for multiple comparisons, rs4532 also showed nominally significant association (p = 0.0261) with BPAQ score.

Conclusions
Our results support that genetic variations of dopamine system may contribute to alcohol cravings and impulsivity in patients with AUD.

INFLUENCE OF DOPAMINE-RELATED GENES ON PROBLEMATIC DRINKINGS, IMPULSIVITY AND AGGRESSION IN KOREAN MALE PATIENTS WITH ALCOHOL USE DISORDER