Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption

Alcohol Alcohol. 2010 Jul-Aug;45(4):303-11. doi: 10.1093/alcalc/agq035. Epub 2010 Jun 16.

Abstract

Aims: Circadian clock genes are involved in the development of drug-induced behaviors and regulate neurotransmission pathways in addiction. Our aim was to study whether circadian clock gene polymorphisms predispose to alcohol dependence or abuse or other alcohol-related characteristics.

Methods: The study sample comprised of 512 individuals having alcohol dependence or alcohol abuse (according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)) and their 511 age- and sex-matched controls. This population-based sample was drawn from a cohort (n = 7415), representative of the Finnish general population aged 30 and over. Altogether 42 single-nucleotide polymorphisms of 19 genes related to the circadian pacemaker system were genotyped.

Results: ARNTL rs6486120 T(+) allelic status (P = 0.0007, q = 0.17), ADCYAP1 rs2856966 GG genotype (P = 0.0006, q = 0.17) and VIP CC haplotype (rs3823082-rs688136) (P = 0.0006) were suggestively associated with alcohol consumption in socially drinking controls. ARNTL2 GT haplotype (rs7958822-rs4964057) associated suggestively with alcohol abuse diagnosis (P = 0.0013). Earlier findings on the associations of DRD2 and NPY with alcohol dependence were supported: DRD2/ANKK1 Taq1A(1) increased (P = 0.04) and NPY Pro7 decreased (P = 0.01) the risk of alcohol dependence.

Conclusions: ARNTL, ARNTL2, VIP and ADCYAP1 were indicated as having influence on alcohol use or abuse. The role of DRD2 and NPY on alcohol dependence was also supported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Adult
  • Alcohol Drinking / genetics*
  • Alcoholism / genetics*
  • CLOCK Proteins / genetics
  • Circadian Rhythm / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Interview, Psychological
  • Male
  • Middle Aged
  • Pituitary Adenylate Cyclase-Activating Polypeptide / genetics
  • Polymorphism, Single Nucleotide*
  • Vasoactive Intestinal Peptide / genetics

Substances

  • ADCYAP1 protein, human
  • ARNTL Transcription Factors
  • BMAL1 protein, human
  • BMAL2 protein, human
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Vasoactive Intestinal Peptide
  • CLOCK Proteins
  • CLOCK protein, human