Impulsivity and aggression in alcohol withdrawal syndrome is modulated by the interaction of ZNF804A and mTOR polymorphism

Pharmacol Biochem Behav. 2024 Mar:236:173708. doi: 10.1016/j.pbb.2024.173708. Epub 2024 Jan 10.

Abstract

Alcohol withdrawal syndrome (AWS) is a poorly studied phenotype of alcohol use disorder. Understanding the relationship between allelic interactions and AWS-related impulsivity and aggression could have significant implications. This study aimed to investigate the main and interacting effects of ZNF804A and mTOR on impulsivity and aggression during alcohol withdrawal. 446 Chinese Han adult males with alcohol dependence were included in the study. Impulsivity and aggression were assessed, and genomic DNA was genotyped. Single gene analysis showed that ZNF804A rs1344706 (A allele/CC homozygote) and mTOR rs1057079 (C allele/TT homozygote) were strongly associated with AWS-related impulsivity and aggression. In the allelic group, MANOVA revealed a significant gene x gene interaction, suggesting that risk varied systematically depending on both ZNF804A and mTOR alleles. Additionally, a significant interactive effect of ZNF804A rs1344706 and mTOR rs7525957 was found on motor impulsivity and physical aggression, and the ZNF804A rs1344706 gene variant had significant effects on motor impulsivity and physical aggression only in mTOR rs7525957 TT homozygous carriers. The study showed that specific allelic combinations of ZNF804A and mTOR may have protective or risk-enhancing effects on AWS-related impulsivity and aggression.

Keywords: Aggression; Alcohol withdrawal syndrome; Impulsivity; Single nucleotide polymorphism; ZNF804A.

MeSH terms

  • Adult
  • Aggression
  • Alcoholism* / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Impulsive Behavior
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Polymorphism, Single Nucleotide
  • Schizophrenia* / genetics
  • Substance Withdrawal Syndrome* / genetics
  • TOR Serine-Threonine Kinases / genetics

Substances

  • TOR Serine-Threonine Kinases
  • ZNF804A protein, human
  • Kruppel-Like Transcription Factors