Several clock genes polymorphisms are meaningful risk factors in the development and severity of cannabis addiction

Chronobiol Int. 2019 Jan;36(1):122-134. doi: 10.1080/07420528.2018.1523797. Epub 2018 Dec 11.

Abstract

Circadian rhythms have been related to psychiatric diseases and regulation of dopaminergic transmission, especially in substance abusers. The relationship between them remained enigmatic and no data on the role of clock genes on cannabis dependence have been documented. We aimed at exploring the role of clock gene genotypes as potential predisposing factor to cannabis addiction, using a high throughput mass spectrometry methodology that enables the large-scale analysis of the known relevant polymorphisms of the clock genes. We have conducted a case-control study on 177 Caucasians categorizing between cannabis-addicted subjects and casual consumers based on structured interviews recorded socio-demographic data, AUDIT, Fagerström test, MINI, and medical examinations. Alcohol, opiates, and stimulants' consumption was as exclusion criteria. We report an association between several Single Nucleotide Polymorphism (SNP)s in main circadian genes SNPs, especially the gene locus HES7/PER1 on chromosome 17 and cannabis consumption as well as the development of neuropsychiatric and social disorders. This SNP's signature that may represent a meaningful risk factor in the development of cannabis dependence and its severity requires to be deeply explored in a prospective study.

Keywords: Addiction; cannabis; circadian; clock genes; polymorphisms.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Case-Control Studies
  • Female
  • Gene Expression Profiling / methods
  • Genetic Predisposition to Disease
  • Haplotypes
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Linkage Disequilibrium
  • Male
  • Marijuana Abuse / ethnology
  • Marijuana Abuse / genetics*
  • Marijuana Smoking / ethnology
  • Marijuana Smoking / genetics*
  • Middle Aged
  • Period Circadian Proteins / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Severity of Illness Index
  • Transcriptome
  • White People / genetics
  • Young Adult

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • HES7 protein, human
  • PER1 protein, human
  • Period Circadian Proteins