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Related Experiment Video

Updated: Mar 29, 2026

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Differential gene expression patterns between smokers and non-smokers: cause or consequence?

Jacqueline M Vink1,2,3, Rick Jansen2,4, Andy Brooks5

  • 1Department of Biological Psychology, VU University, Amsterdam, The Netherlands.

Addiction Biology
|November 24, 2015
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Smoking significantly alters gene expression, impacting immune and cancer pathways. Most gene expression changes are reversible upon quitting, though some DNA variants may influence smoking behavior.

Keywords:
gene expressiongenome widesmoking

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Area of Science:

  • Genomics
  • Molecular Biology
  • Public Health

Background:

  • The molecular basis of smoking-induced health issues remains largely unknown.
  • Understanding gene expression changes associated with smoking is crucial for public health interventions.

Purpose of the Study:

  • To identify molecular pathways affected by smoking behavior through genome-wide gene expression analysis.
  • To determine the reversibility of smoking-induced gene expression changes and explore potential genetic influences on smoking behavior.

Main Methods:

  • Genome-wide gene expression profiling in peripheral blood samples from smokers, ex-smokers, and never-smokers.
  • Analysis of data from two large population-based cohorts and monozygotic twin pairs discordant for smoking.
  • Classification of gene expression changes based on reversibility after smoking cessation and association analysis with genetic variants.

Main Results:

  • 132 genes were found to be differentially expressed between current smokers and never-smokers, notably G protein-coupled receptor 15 and leucine-rich repeat neuronal 3.
  • Enrichment analysis revealed smoking-related genes are involved in immune system, blood coagulation, natural killer cell, and cancer pathways.
  • The majority of altered gene expression (94 genes) were reversible, 31 were slowly reversible, and 6 were irreversible after smoking cessation. Genetic variants in GPR56 and RARRES3 were associated with smoking intensity.

Conclusions:

  • Smoking induces extensive differential gene expression patterns that are primarily direct consequences of smoking and largely reversible upon cessation.
  • Identified gene expression changes are clustered in pathways relevant to smoking-related diseases.
  • Genetic variants may influence smoking behavior through mediating gene expression, suggesting a complex interplay between genes and smoking.